DEPARTMENT OF HEALTH AND HUMAN SERVICES 

CENTERS FOR DISEASE CONTROL AND PREVENTION

Advisory Committee on 

Immunization Practices (ACIP)

Summary Report

October 21, 2015

Atlanta, Georgia 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

2 

Table of Contents Page

Agenda 4-6 

Acronyms 7-10

Welcome and Introductions 11-16

Agency Updates

 Centers for Disease Control and Prevention (CDC)

 Center for Medicare and Medicaid Services (CMS)

 Department of Defense (DoD)

 Department of Veteran’s Affairs (DVA)

 Food and Drug Administration (FDA)

 Heath Resources and Services Administration (HRSA)

 Indian Health Services (I HS)

 National Institutes of Health (NIH)

 National Vaccine Advisory Committee (NVAC)

 National Vaccine Program Office (NVPO)

16-19

Child and Adolescent Immunization Schedule

 Introduction

 2016 Child and Adolescent Immunization Schedule

19-24

Adult Immunization Schedule

 Introduction

 Erratum in 2015 Adult Immunization Schedule

 2016 Adult Immunization Schedule

24-29

Meningococcal Vaccine

 Introduction

 Serogroup C Outbreak among Men Who Have Sex with Men (MSM), Chicago 2015

30-40

Influenza

 Introduction

 Epidemiology and Surveillance Update

 Cost-Effectiveness of High-Dose Versus Standard-Dose Inactivated Influenza Vaccine in Adults Aged 

65 and Older

 Adjuvanted Trivalent Influenza Vaccine

40-55

Vaccine Supply 55-58

Human Papillomavirus (HPV) Vaccines

 Introduction

 HPV Vaccine Coverage in the US, NIS-Teen 2014

 Programmatic Strategies to Increase HPV Vaccine Coverage 

 Update on HPV Vaccine Safety

 Monitoring Impact of the HPV Vaccination Program

 HPV Vaccines Work Group Plans

58-77

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

3 

Japanese Encephalitis (JE) Vaccine

 Introduction

 Change in JE Vaccine Distributor

 Immunogenicity in Older Adults

 Co-Administration with Rabies Vaccine

 Alternative Dosing Schedule

 JE Vaccine Work Group Plans

77-85

Combination Vaccines

 Introduction

 Pediatric Hexavalent Vaccine (DTaP-IVP-Hib-HepB), Merck/Sanofi

85-91

Cholera Vaccine

 Introduction

 Cholera in US Travelers

91-97

Ebola Vaccine Trial Update 97-104

Public Comment 106-108

Certification 109

Membership Roster 110-118

Appendix A: Public Comment Letter Received 119-122

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

4 

MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)

Centers for Disease Control and Prevention

1600 Clifton Road, NE, Tom Harkin Global Communications Center, Kent "Oz" Nelson Auditorium

Atlanta, Georgia 30329 

October 21, 2015 (1-day meeting)

AGENDA ITEM PURPOSE PRESIDER/PRESENTER(s)

Wednesday, October 21st 

8:00 Welcome & 

Introductions

Dr. Nancy Bennett (ACIP Chair)

Dr. Ray Strikas (Acting ACIP 

Executive Secretary; CDC)

8:30 Agency Updates

CDC, CMS, DoD, DVA, FDA, HRSA, IHS, NIH, 

NVPO

Information CDC and ex officio members

 

8:45 Child and Adolescent Immunization 

Schedule

Introduction Information, 

Discussion 

Vote 

Dr. Jose Romero (ACIP, WG 

Chair)

Dr. Candice Robinson 

(CDC/NCIRD)

2016 child and adolescent immunization

schedule

9:30 Adult Immunization Schedule

Introduction Information 

& Discussion

Dr. Kathleen Harriman (ACIP, 

WG Chair)

Erratum in 2015 adult immunization Dr. David Kim (CDC/NCIRD) 

schedule 

2016 adult immunization schedule update Vote

10:00 Break 

10:30 Meningococcal Vaccines

Introduction

Serogroup C outbreak among men who 

have sex with men (MSM), Chicago, 2015

 

Information 

& Discussion

Dr. Lorry Rubin (ACIP, WG 

Chair)

Dr. Sarah Kemble (Chicago 

DPH) 

11:15 Influenza

Introduction

Epidemiology and surveillance Update 

Cost-effectiveness of high-dose versus 

standard-dose inactivated influenza vaccine 

in adults aged 65 years and older

Adjuvanted trivalent influenza vaccine 

 

Information 

& Discussion

Dr. Ruth Karron (ACIP, WG 

Chair)

Ms. Lynnette Brammer 

(CDC/NCIRD)

Dr. Ayman Chit (Sanofi 

Pasteur)

Dr. Kelly Lindert (NVS Influenza 

 Vaccines)

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

12:15 Vaccine 

Supply

5 

Dr. Lorry Rubin (ACIP, WG 

Chair)

Dr. Katrin Dubischar (Valneva)

Dr. Susan Hills (CDC/NCEZID)

 

Dr. Art Reingold (ACIP, WG 

Chair)

Dr. Andrew Lee (Merck)

Dr. Jeanne Santoli 

(CDC/NCIRD)

 

 

 

12:20 Lunch

1:35 Human Papillomavirus (HPV) Vaccines

Introduction

HPV vaccine coverage in the US, NIS-Teen 

2014

Programmatic strategies to increase HPV 

vaccine coverage 

Update on HPV vaccine safety 

Monitoring impact of the HPV vaccination 

program

HPV Vaccines Work Group plans

Information 

& Discussion

Dr. Allison Kempe (ACIP, WG 

Chair)

Dr. Sarah Reagan-Steiner 

(CDC/NCIRD)

Dr. Robin Curtis (CDC/NCIRD)

Dr. Lakshmi Sukumaran, 

(CDC/NCEZID)

Dr. Lauri Markowitz 

(CDC/NCHHSTP)

Dr. Lauri Markowitz 

(CDC/NCHHSTP)

 

2:35 Japanese Encephalitis (JE) Vaccine

Introduction

Change in JE vaccine distributor; 

immunogenicity in older adults; coadministration with rabies vaccine; 

alternative dosing schedule

JE Vaccine Work Group plans

Information 

& Discussion

3:25 Break

3:50 Combination Vaccine

Introduction

Pediatric hexavalent vaccine (DTaP-IPV-HibHepB), Merck/Sanofi

Information 

& Discussion

4:35 Cholera 

Vaccine

Introduction

Cholera in U.S. travelers

Information 

& Discussion

Dr. Art Reingold (ACIP, WG 

Chair)

Dr. Karen Wong (CDC/NCEZID) 

5:10 Ebola Vaccine Trial Update Information Dr. Susan Goldstein, CDC Ebola 

Response Team

5:45 Public 

Comment

6:00 Adjourn

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

6 

Acronyms

CDC Centers for Disease Control & Prevention

CMS Centers for Medicare and Medicaid Services 

DoD Department of Defense

DTaP-IPV-HibHepBDiphtheria, tetanus, acellular pertussis, inactivated polio, Haemophilus influenzae type 

B and hepatitis B

DVA Department of Veterans Affairs

FDA Food and Drug Administration

GRADE Grading of Recommendations Assessment, Development and Evaluation

HRSA Health Resources and Services Administration

IHS Indian Health Service

MSM Men who have sex with men

NCHHSTP National Center for HIV, Hepatitis, STD and TB Prevention [of CDC/OID] 

NCIRD CDC National Center for Immunization & Respiratory Diseases [of CDC/OID] 

NCEZID National Center for Emerging and Zoonotic Diseases [of CDC/OID]

NIH National Institutes of Health

NIS National Immunization Survey

NVPO National Vaccine Program Office

VFC Vaccines for Children

WG Work Group

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

7 

Acronyms Used in This Document

AAFP American Academy of Family Physicians 

AAP American Academy of Pediatrics

ACA Affordable Care Act

ACIP Advisory Committee on Immunization Practices

ACNM American College of Nurse Midwives 

ACOG American Congress of Obstetricians and Gynecologists 

ACP American College of Physicians 

ACS American Cancer Society 

AE Adverse Events

AFIX Assessment, Feedback, Incentives, and eXchange 

AFP American Family Physicians

aHCST Autologous Hematopoietic Stem Cell Transplant 

AMA American Medical Association

ANA American Nurses Association 

APA Academic Pediatric Association 

APD Adequate Provider Data 

ASTHO Association of State and Territorial Health Officials 

aTIV Adjuvanted Trivalent Inactivated Influenza Viral Vaccine 

BARDA Biomedical Advanced Research and Development Authority 

BIO Biotechnology Industry Organization 

BLA Biologics License Application 

CBER Center for Biologics Evaluation and Research 

CBO Community-Based Organization 

CCH Center for Community Health (URMC)

CDC Centers for Disease Control and Prevention

CDPH Chicago Department of Public Health 

ChAd3-EBO Z Chimpanzee Adenovirus 3-Based Vaccine

CICP Countermeasures Injury Compensation Program 

CID Clinical Infectious Diseases 

CIN Cervical Intraepithelial Neoplasia 

CISA Project Clinical Immunization Safety Assessment Project

CMS Center for Medicare and Medicaid

COI Conflict of Interest 

COID Committee on Infectious Disease, AAP 

COMAHS College of Medicine and Allied Health Sciences 

CRPS Complex Regional Pain Syndrome 

CSF Cerebrospinal Fluid 

CSTE Council of State and Territorial Epidemiologists 

CTSI Clinical & Translational Science Institute (URMC)

CVD Cardiovascular Disease 

DC District of Columbia

DCPC Division of Cancer Prevention and Control 

DM Diabetes Mellitus

DNA deoxyribonucleic acid 

DoD Department of Defense

DSMB Data Safety Monitoring Board 

DVA Department of Veterans Affairs

EBR Evidence-Based Recommendations 

ED Emergency Department 

EHR Electronic Health Record 

EIP Emerging Infections Program 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

8 

EIS Epidemic Intelligence Service 

EMA European Medicines Agency 

ENT Ear, Nose, and Throat 

Epi-X Epidemic Information Exchange 

ETEC Enterotoxigenic E. coli

EU European Union

EVD Ebola Virus Disease 

FDA Food and Drug Administration

FHA Filamentous Hemagglutinin 

FLU VE Influenza Vaccine Effectiveness Network

FOA Funding Opportunity Announcement 

FY Fiscal Year

GBS Guillain-Barré Syndrome 

GDPH Georgia Department of Public Health 

GEVIT Global Ebola Vaccine Implementation Team 

GMC Geometric Mean Concentrations 

GMT Geometric Mean Titers 

GRADE Grading of Recommendation Assessment, Development and Evaluation 

GSK GlaxoSmithKline 

HAN Health Alert Network 

HBsAG Hepatitis B Surface Antigen 

HCP Healthcare Personnel 

HCW Healthcare Workers 

HCV Hepatitis C Virus 

HD-IIV High-Dose Inactivated Influenza Vaccine 

HEDIS Healthcare Effectiveness Data and Information Set 

HI Hemagglutination Inhibition 

Hib Haemophilus influenzae type b 

HPV Human Papillomavirus

HRSA Health Resources and Services Administration 

HSCT Hematopoietic Stem Cell Transplantation 

HV Hexavalent 

IDSA Infectious Disease Society of America 

IgA Immunoglobulin A

IHS Indian Health Service 

IIS Immunization Information System 

IIV Inactivated Influenza Vaccine 

ILI Influenza-Like Illness

ILINet Influenza-Like Illness Surveillance Network

IM Intramuscularly 

IMD Invasive Meningococcal Disease 

IND Investigational New Drug 

IOM Institute of Medicine 

IPD Invasive Pneumococcal Disease 

ISD Immunization Services Division 

ISO Immunization Safety Office 

IT Information Technology 

JE Japanese Encephalitis

JE-MB Inactivated Mouse Brain–Derived Japanese Encephalitis Vaccine 

JE-VC Vero Cell Culture-Derived Japanese Encephalitis Vaccine 

LAIV Live Attenuated Influenza Vaccine 

LCI Laboratory-Confirmed Influenza 

LGBT Lesbian, Gay, Bisexual, and Transgender 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

9 

LIVE Lombardia Influenza Vaccine Effectiveness Study

LMP Last Menstrual Period 

LPS Lipopolysaccharide 

LY Life Years 

MCHS Marshfield Clinic Health System 

MenACWY Quadrivalent Meningococcal Conjugate Vaccine

MenB Serogroup B Meningococcal Disease

MLST Multi-Locus Sequence Type 

MMR Measles, Mumps, Rubella

MMWR Morbidity and Mortality Weekly Report

MOHS Ministry of Health and Sanitation 

MPSV4 Meningococcal Polysaccharide Vaccine 

MSM Men Who Have Sex With Men 

NACCHO National Association of County and City Health Officials 

NAO National Area Health Education Center Organization 

NCEZID National Center for Emerging and Zoonotic Infectious Diseases

NCHHSTP National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention 

NCHS National Center for Health Statistics 

NCIRD National Center for Immunization and Respiratory Diseases 

NEJM New England Journal of Medicine 

NHANES National Health and Nutrition Examination Survey 

NHIS National Health Interview Survey

NHRC Naval Health Research Center 

NIAID National Institute of Allergy and Infectious Diseases 

NIC National Influenza Centre 

NIH National Institutes of Health

NIP National Immunization Program 

NIPH Norwegian Institute of Public Health 

NIS National Immunization Survey 

NMA National Medical Association

NMA National Meningitis Association

NREVSS National Respiratory and Enteric Virus Surveillance System 

NVAC National Vaccine Advisory Committee 

NVPO National Vaccine Program Office 

NYC New York City 

NYU New York University 

OPHSS Office of Public Health Scientific Services 

PCR Polymerase Chain Reaction 

PCV Pneumococcal Conjugate Vaccine 

PEP Post-Exposure Prophylaxis 

PFGE Pulsed-Field Gel Electrophoresis 

PHAC Public Health Agency of Canada 

PhRMA Pharmaceutical Research and Manufacturers of America 

PI Principal Investigator 

PIDS Pediatric Infectious Diseases Society 

POI Primary Ovarian Insufficiency 

PPHF Prevention and Public Health Funds 

PRNT Plaque Reduction Neutralization Test 

PRP-OMPC Polyribosylribitol Phosphate Polysaccharide linked to Outer Membrane Protein Complex 

PRP-T Polyribosylribitol Phosphate Polysaccharide Conjugated to Tetanus Toxoid (Haemophilus B 

Conjugate) 

QALYs Quality Adjusted Life Years 

RCA Rapid Cycle Analysis 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

10 

RCT Randomized Controlled Trial

RDD Random Digit Dial 

RSV Respiratory Syncytial Virus 

rVSV-ZEBOV Recombinant Vesicular Stomatitis Virus Vaccine Expressing the Glycoprotein of Zaire Ebola 

Virus 

SAEs Serious Adverse Events 

SAGE Strategic Advisory Group of Experts (WHO)

SAHM Society for Adolescent Health and Medicine 

SCR Seroconversion Rate 

SD-IIV Standard-Dose Inactivated Influenza Vaccine 

SHEA Society for Healthcare Epidemiology of America 

SME Subject Matter Experts 

SNP Single Nucleotide Polymorphism 

STI Sexually Transmitted Infection 

STRIVE Sierra Leone Trial to Introduce a Vaccine against Ebola 

Tdap Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis

TIV Trivalent Influenza Vaccine

TIV-HD Trivalent, Inactivated Influenza Vaccine 

UK United Kingdom

UNICEF United Nations International Children's Emergency Fund 

URMC University of Rochester Medical Center 

US United States

USAID United States Agency for International Development 

USPHS United States Public Health Service

VAERS Vaccine Adverse Event Reporting System

VBYG Vaccinate Before You Graduate 

VE Vaccine Effectiveness

VFC Vaccines for Children

VHA Veterans Health Administration 

VICP (National) Vaccine Injury Compensation Program 

VRBPAC Vaccines and Related Biological Products Advisory Committee

VSD Vaccine Safety Datalink

VSVdeltaGZEBOVVesicular Stomatitis Virus-Based Vaccine

VTE Venous Thromboembolism 

WG Work Group

WGS Whole Genome Sequencing 

WHO World Health Organization

WNV West Nile Virus 

YF Yellow Fever

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

11 

Welcome and Introductions

Nancy Bennett, MD, MS

ACIP Chair

Raymond A. Strikas, MD, MPH, FACP

Acting Executive Secretary, ACIP / CDC

Following Dr. Bennett’s greeting and call to order, Dr. Strikas welcomed everyone to the 

October 2015 Advisory Committee on Immunization Practices (ACIP) meeting. He indicated 

that the proceedings of this meeting would be accessible to people not in attendance via the 

World Wide Web, and welcomed those who could not attend the meeting in person. He then

recognized several others in the room who were to be present throughout the duration of the 

meeting to assist with various meeting functions: Stephanie Thomas, Natalie Greene, and Chris 

Caraway.

 

Regarding staffing changes, Dr. Strikas announced that Dr. Anne Schuchat, formerly Director of 

the National Center for Immunization and Respiratory Diseases (NCIRD) and a fixture of the 

ACIP meetings for the last 10 or more years, had been appointed Principal Deputy Director of 

CDC. Dr. Rima Khabbaz is now Acting Director of NCIRD. Dr. Khabbaz and Dr. Nancy 

Messonnier were both present during this meeting. Key staff member of the ACIP Secretariat, 

Dr. Jean Smith, was not present as she was tending to an ill family member.

Dr. Strikas noted that handouts of the presentations were distributed to the ACIP members and 

were made available for others on the tables outside of the auditorium. Slides presented during 

this meeting will be posted on the ACIP website approximately two weeks after the meeting 

concludes, the live webcast will be posted within four weeks following the meeting, and the 

meeting minutes will be available on the website within approximately 90 days following this 

meeting. Members of the press interested in conducting interviews with ACIP members were 

instructed to contact Ian Branam, located at the Press table, for assistance in arranging 

interviews. 

The next ACIP meeting will convene at CDC on Wednesday and Thursday, February 24-25, 

2016. Registration for all meeting attendees is required and will be open Wednesday, October 

21, 2015 on the ACIP website. The registration deadline for Non-US citizens is February 3, 

2016 and for US citizens registration closes February 10, 2016. Registration is not required for 

webcast viewing. As a reminder for non-US citizens attending ACIP meetings, completion of 

several forms is required for each meeting at the time of registration. It is important that these 

forms be submitted within the required time frame. Stephanie Thomas, the ACIP Committee 

Management Specialist, will be able to help with any questions about the process.

Welcome, Introductions, & Greetings from Dr. Schuchat

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

12 

 Dr. Nancy Bennett

Dr. Strikas then introduced the new ACIP Chair, Dr. Nancy Bennett. Dr. Bennett will serve as 

Chair from this meeting through June 2018. Dr. Bennett is Professor of Medicine and Public 

Health Sciences at the Center for Community Health (CCH) and Co-Director of the Clinical & 

Translational Science Institute (CTSI) within the University of Rochester Medical Center 

(URMC) School of Medicine and Dentistry (SMD). She graduated from New York University 

(NYU) School of Medicine, and completed her Internal Medicine Residency and Chief 

Residency at Bellevue Hospital in New York City (NYC). She also completed a fellowship in 

general medicine, including a Master’s Degree in Epidemiology, and served on the faculty at 

Columbia University College of Physicians and Surgeons before moving to Rochester. She 

served as Deputy Health Director of Monroe County Department of Public Health for 16 years 

before returning to URMC where she is currently the Director of the CCH and a Principal 

Investigator (PI) of the URMC CTSI. Since 1997, she has been the PI for the Rochester 

Emerging Infections Program (EIP) Region, and has led a variety of supplemental projects 

related to pneumococcal and influenza surveillance and prevention. Dr. Bennett served as the 

National Association of County and City Health Officials (NACCHO) liaison member to ACIP 

from 2004 through 2007, and has been a voting member of ACIP since 2011. For the past two 

years, she has served as the unofficial Vice-Chair of ACIP. 

Dr. Bennett emphasized what a pleasure it was to serve as ACIP Chair. She has been 

attending ACIP meetings for many years, and participating as a voting member for the last few 

years and said that it is probably the most interesting and challenging work that she does. It 

has been a great honor and privilege, and she is very happy to be the new Chair. She said she 

thought the most important words she could convey is that she is available at all times to 

address the needs of the ACIP and its members . She invited input regarding ways to make 

ACIP run more smoothly, be more accountable, and make the best possible recommendations. 

She tends to believe in “servant leadership,” which means making it possible for everyone to do 

their very best, which she perceives to be her job as the ACIP Chair—to help the members lead 

the committee rather than to lead them. She thanked everyone for this honor. Dr. Bennett then 

introduced and welcomed the following new ACIP members:

 Dr. Echezona Ezeanolue

Professor of Pediatrics and Public Health

Director, Global Health and Implementation Research Initiatives

School of Community Health Sciences

University of Nevada, Las Vegas

 Dr. Kelly Moore

Director, Tennessee Immunization Program

Tennessee Department of Health

Assistant Clinical Professor, Department of Health Policy

Vanderbilt University School of Medicine

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

13 

 Dr. Emmanuel (Chip) Walter 

Professor of Pediatrics

Duke University School of Medicine

 Dr. David Stephens 

Professor of Medicine, Division of Infectious Diseases

Chair, Department of Medicine

Emory University School of Medicine

Dr. Strikas made the following announcements regarding Ex Officio members: 

 Dr. Narayan Nair, representing the Health Resources and Services Administration (HRSA), 

was in attendance

 Dr. Linda Kinsinger, Veterans Health Administration (VHA), was unable to attend 

He made the following announcements regarding Liaison Representatives in attendance: 

 Dr. Leonard Friedland, GlaxoSmithKline (GSK), representing the Biotechnology Industry 

Organization (BIO) 

 Dr. Kimberly Martin, representing the Association of State & Territorial Health Officials 

(ASTHO) 

 Dr. David Johnson from Sanofi Pasteur, representing the Pharmaceutical Research and 

Manufacturers of America (PhRMA), who will now serve as the regular PhRMA liaison 

member

Regarding public comments, Dr. Strikas indicated that topics presented during ACIP meetings 

include open discussion with time reserved for public comment. He explained that time for 

public comment pertaining to topics on the agenda was scheduled following the end of the day’s 

sessions, and that time for public comments also may be provided prior to specific votes by 

ACIP to enable these comments to be considered before the vote. During this meeting, there 

was one public comment opportunity at 5:45 PM. People who planned to make public 

comments were instructed to visit the registration table at the rear of the auditorium where Ms. 

Stephanie Thomas would record their name and provide information on the process. People 

making public comments were instructed to provide 3 pieces of information: name, organization 

if applicable, and any conflicts of interest (COI). Registration for public comment also was 

solicited in advance of this meeting through the Federal Register. Given time constraints, each 

comment was limited to 3 minutes. Participants unable to present comments during this 

meeting were invited to submit their comments in writing for inclusion in the meeting minutes.

Regarding recommendations, ACIP uses a standard process to systematically collect and 

evaluate evidence behind each recommendation. More information about the Grading of 

Recommendation Assessment, Development and Evaluation (GRADE) process can be found 

on the ACIP website. Key factors for developing recommendations include the balance of 

benefits and harms, type or quality of evidence, values and preferences, and health economic 

analyses. The ACIP recommendation categories are: 

 Category A: A recommendation that applies to all persons in an age- or risk-based group.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

14 

 Category B: A recommendation for individual clinical decision making.

 No recommendation for an unresolved issue. 

Vaccine safety issues will continue to be presented at every ACIP meeting. During this 

meeting, these issues were included as part of specific topic presentations.

Regarding ACIP implications of the Affordable Care Act (ACA), ACIP recommendations become 

policy following approval by the CDC Director and publication in the Morbidity and Mortality 

Weekly Report (MMWR). The ACA was enacted in 2010, and requires insurance coverage for 

recommended immunizations without copays/deductibles when provided by an in-network 

provider. Health plans have one plan year from MMWR publication to implement 

recommendations according to CDC immunization schedules, including recommendations 

illustrated in the graphics and those described in footnotes.

During every meeting, an update is provided on the status of ACIP recommendations. There 

have been three ACIP publications since June 2015, with one additional publication to be 

published this week, which are reflected in the following table: 

Recommendations and immunization schedules can be downloaded from the ACIP website. 

ACIP has a policy that every three to five years each recommendation is reviewed, and then 

renewed, revised, or retired.

Applications for ACIP membership are due no later than November 13, 2015 for the 4-year term 

beginning July 1, 2016. Detailed instructions for submission of names of potential candidates to 

serve as ACIP members may be found on the ACIP web site:

E-mail: acip@cdc.gov Web homepage: http://www.cdc.gov/vaccines/acip/index.html

Nominations: http://www.cdc.gov/vaccines/acip/committee/req-nominate.html

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

15 

A current CV, at least one recommendation letter from a non-federal government employee, and 

complete contact information are required. These may be submitted as e-mail attachments to 

Dr. Jean Clare Smith at jsmith2@cdc.gov

To summarize COI provisions applicable to the ACIP, as noted in the ACIP Policies and 

Procedures manual, members of the ACIP agree to forgo participation in certain activities 

related to vaccines during their tenure on the committee. For certain other interests that 

potentially enhance a member’s expertise while serving on the committee, CDC has issued 

limited COI waivers. Members who conduct vaccine clinical trials or serve on data safety 

monitoring boards (DSMBs) may present to the committee on matters related to those vaccines, 

but these members are prohibited from participating in committee votes on issues related to 

those vaccines. Regarding other vaccines of the concerned company, a member may 

participate in discussions, with the proviso that he/she abstains on all votes related to the 

vaccines of that company. It is important to note that at the beginning of each meeting, ACIP

members state any COIs. 

Before officially beginning the meeting, Dr. Bennett called the roll to determine whether any 

ACIP members had conflicts of interest. The following conflicts of interest were declared:

 Dr. Belongia: Receives research support from Medimmune and has a conflict for influenza.

 Dr. Walter: Receives research support from Merck for a rotavirus vaccine study, which is 

an investigator-initiated project. 

 The remainder of the ACIP members declared no conflicts.

Dr. Bennett then introduced the ex officio members, and requested that the liaison and ex officio

members introduce themselves.

Greetings from Dr. Schuchat

Anne Schuchat, MD (RADM, USPHS)

Principal Deputy Director

Centers for Disease Control and Prevention and

Agency for Toxic Substances and Disease Registry

Dr. Schuchat said it was such a pleasure to welcome everyone to the October 2015 ACIP 

meeting. Since February 2006 three times a year, she has participated in the extraordinary 

work of ACIP. She particularly welcomed new members, Drs. Ezeanolue, Moore, Stephens, 

and Walter. She thanked them in advance for the extraordinary effort they would put into ACIP. 

She also thanked the existing members for their hard work and the wisdom and expertise that 

they bring to this role. She was thinking about ACIP now that she is in the nostalgic phase of 

her CDC career, and realized that ACIP is the exact opposite of Las Vegas. What happens in 

this room does not stay in this room. In fact, it is being webcast all over the world and has 

impact in every family in America and in many communities around the world. The way ACIP 

reviews the evidence and deliberates on highly difficult issues has an impact for every practice, 

and on immunization policies in America and many other countries. She knows how much work 

it is to serve on ACIP and for CDC staff to support the work groups (WGs) and ACIP in general. 

She thanked everyone for what they do, and encouraged them to be serious, deliberate, and 

continue their extraordinary work for this nation.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

16 

 

Centers for Disease Control and Prevention (CDC)

Dr. Khabbaz said that it was a privilege to be serving as Acting Director of NCIRD with an 

outstanding Deputy Director, Dr. Nancy Messonier, and a great leadership team. NCIRD has 

established a search committee for a permanent Director that is chaired by Dr. Chesley 

Richards, Deputy Director of the Office of Public Health Scientific Services (OPHSS). Also 

serving on the search committee are Dr. Walter Orenstein and Dr. William Schaffner. The hope 

is to have the position vacancy posted soon. This is a great center for a good slate of highly 

qualified candidates. Dr. Khabbaz also announced that the National Immunization Conference 

is scheduled for September 13-15, 2016 in Atlanta, Georgia. This is a key conference of 

immunization partners to discuss science, policy, education, and other aspects related to 

vaccine-preventable diseases. She expressed gratitude to Dr. Strikas for serving as Acting 

Executive Secretary for ACIP, and noted that CDC would soon be announcing a permanent 

Executive Secretary.

Centers for Medicare and Medicaid Services (CMS)

Dr. Hance announced that CMS has developed a toolkit of outreach materials focused on 

preventive services for adults. CMS realized that as the number of adults in the Medicaid 

program has expanded, there are limited materials focused on adults. The materials in the 

toolkit emphasize the need to obtain basic preventive services, including immunizations. The 

toolkit has been very well-received. Again this year, CMS is working with the National Vaccine 

Program Office (NVPO) to track the prevalence of Medicare influenza vaccines this season. 

The interactive mapping tool on NVPO’s website provides information on the number of fee-forservice Medicare beneficiaries who have obtained an influenza vaccine using claims data. The 

data are obtained weekly.

Department of Defense (DoD)

Dr. Sergienko reported that the Department of Defense (DoD) has begun its seasonal influenza 

vaccination program. Influenza vaccine is mandatory for all uniformed personnel, including 

Active Duty, Coast Guard, Reserve, and National Guardsmen. DoD’s immunization goal is 90% 

by mid-December. In addition, influenza vaccination is mandatory for all healthcare personnel 

(HCP) who provide direct patient care in military facilities and is also recommended for all other 

HCP within the military healthcare system. To meet this demand, DoD ordered more than 3.6 

million doses of vaccine to be distributed throughout its locations in the United States (US) and 

overseas and to ships afloat. The first meeting of the Vaccine Hesitancy Working Group was 

convened on August 26, 2015. That group is working to identify topics to increase uptake of 

vaccines among DoD beneficiaries. DoD is conducting a carriage study of most military 

personnel for meningococcal disease. That is being conducted through the Naval Health 

Research Center (NHRC) with the intent to identify DoD’s baseline carriage and the impact 

potential vaccinations in that population. Dr. Sergienko thanked ACIP for allowing participation 

of DoD subject matter experts (SMEs) within the Maternal Immunization, Cholera, Meningitis, 

and Smallpox WGs. Since the June 2015 meeting, the bid was announced for the electronic 

health record (EHR) that the DoD will be adopting. DoD will be working with CDC to ensure 

that, as best possible, state registry data can be captured within the EHR and vice versa.

Agency Updates

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

17 

Food and Drug Administration (FDA) 

Dr. Sun reported that the Food and Drug Administration (FDA) convened a Vaccine Advisory 

Committee meeting on September 15, 2015 to discuss the safety and effectiveness of the 

adjuvanted seasonal influenza vaccine that is under review currently at FDA. Another Vaccine 

Advisory Committee meeting will be convened on November 13, 2015 specifically devoted to 

the topic of maternal immunization, given the full range of vaccines that are being used and 

being considered for use during pregnancy: influenza, pertussis, respiratory syncytial virus 

(RSV), Group B streptococcus, and others. The Center for Biologics Evaluation and Research 

(CBER) is in a transition phase as the Center Director announced her plans to retire and a 

search for a new Center Director is underway.

Health Resources and Services Administration (HRSA)

Dr. Nair reported that the National Vaccine Injury Compensation Program (VICP) had a very 

busy fiscal year (FY) 2015 with 802 claims filed and 526 claims adjudicated, of which 449 were 

compensable and 77 were dismissed. $204 million in awards were paid to petitioners, and over 

$20.6 million was paid in attorney fees. More data about this program can be obtained on the 

website. Development was completed of proposed recommendations to make several changes 

to the Vaccine Injury Table. The Notice of Proposed Rulemaking was posted for public 

comment on July 29, 2015 to be available for 180 days. A Final Rule proposing to add 

intussusception as an injury associated with rotavirus vaccine was published in the Federal 

Registry in June 2015. In August 2015, the Pandemic Influenza Injury Table Final Rule was 

published in the Federal Registry. In FY 2015, the Countermeasures Injury Table 

Compensation Program (CICP) has compensated 4 claims totaling $2.3 million. VICP and 

CICP are focused on outreach efforts to make providers and the public aware of these safety 

net programs.

 

Indian Health Services (IHS)

Ms. Groom reported that after several seasons of a voluntary comprehensive influenza 

vaccination program for Indian Health Services (IHS) HCP and stagnant rates among HCP, IHS 

has moved forward with a mandatory influenza vaccination policy. This policy is currently 

implemented for IHS’s non-bargaining union employees, and the IHS is working with its unions 

now and hope to have this fully implemented this influenza season. In terms of maternal 

immunization, IHS has developed a performance measure for the agency to start tracking Tdap

(tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) and influenza vaccination of 

pregnant women, and are hoping this will help them with a reminder in the IHS EHR.

National Institutes of Health (NIH) 

Dr. Bennett read the following National Institutes of Health (NIH) update into the record, given 

that Dr. Gorman was unable to attend:

The 2015 Nobel Prize in Chemistry has been awarded to NIH grantees Paul Modrich, PhD of 

the Howard Hughes Medical Institute and Duke University School of Medicine in Durham, North 

Carolina and Aziz Sancar of the University of North Carolina, Chapel Hill, North Carolina for 

having mapped, at a molecular level, how cells repair damaged deoxyribonucleic acid (DNA) 

and safeguard the genetic information. They share the award with Tomas Lindahl of the Francis 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

18 

Crick Institute and Clare Hall Laboratory, Hertfordshire, United Kingdom (UK). The Royal 

Swedish Academy of Sciences said their work on DNA repair “has provided fundamental 

knowledge of how a living cell functions.” From the National Institute of Allergy and Infectious 

Diseases (NIAID), funded researchers at Tulane University developed an experimental aerosol 

vaccine with a modified form of Mycobacterium tuberculosis (Mtb) that was genetically 

engineered to exclude a gene thought necessary for successful lung infection in Maccabees. 

This has been published by Kaushal et al in Nature Communications. Related to RSV, NIAID 

has recently begun testing an RSV challenge study. The strain is a molecularly cloned 

challenge virus, meaning the RSV A2 study virus originates from a single clone of the virus 

strain and has been tested to ensure that it is not contaminated with other infection-causing 

pathogens. NIAID investigators, in collaboration with Hopkins, will analyze participant samples 

to measure levels of virus shedding and immune protection. In addition, FDA and NIAID held a 

workshop in June 2015 that covered constructs, paths forward, obstacles, lessons learned, and 

potential endpoints for RSV candidate vaccines. The agenda and video are available on the 

NIAID website. Related to HIV, an article written about a preventive HIV vaccine has some 

thoughts that are generalizable to the entire field of vaccinology. Since efforts to develop a 

preventive HIV vaccine began in the 1980s, tension has existed between advocates for quickly 

moving vaccine candidates into human testing and those seeking more basic research on HIV 

and immune responses. In a new commentary, scientists from NIH have offered a historic 

perspective on the search for a safe and effective HIV vaccine through the lens of these two 

vaccine development strategies. That article is by Fauci and Marston and can be found in 

Science. A Phase I/II randomized placebo controlled trial in intravenous drug users of an 

hepatitis C virus (HCV) candidate vaccine continues. There is a Phase I trial dose escalating 

trail placebo controlled trial in healthy adults to assess a West Nile Virus (WNV) candidate 

vaccine, for which the primary objectives are to assess safety, reactogenicity, tolerability, and 

immunogencity. There is also a study of a candidate H7N9 vaccine underway. 

National Vaccine Advisory Committee (NVAC)

Dr. Orenstein reported that the National Vaccine Advisory Committee (NVAC) is also working on 

issues of maternal immunization, and has issued a report on how to improve uptake of current 

recommendations. The second phase of that is to assess the obstacles and barriers to 

developing vaccines intended for vaccination of pregnant women, and how to overcome those. 

NVAC has a workgroup and hopes to have a first set of recommendations focused on 

overcoming obstacles at its February 2016 meeting. McKenzie & Company is performing a 

landscape analysis of vaccine innovation challenges and opportunities. They asked for NVAC 

members to cooperate and potentially be interviewed as they try to develop an analysis and 

potential recommendations to incentivize vaccine innovation. In June 2015, NVAC approved 

the report on the role of vaccines in combating antimicrobial resistant bacteria. Hopefully, that 

report will be published soon in Public Health Reports. NVAC is attempting to develop a liaison 

relationship with the committee that is dealing with combating antimicrobial resistant bacteria, 

having one of them on the NVAC committee and an NVAC member on that committee.

National Vaccine Program Office (NVPO) 

Dr. Gellin noted that the National Vaccine Program Office (NVPO) is now 5 years into the 10-

year National Vaccine Plan (NVP), and is in the process of conducting a mid-course review. 

There is a survey on the NVPO website, and there will be conversations about it as well. He 

invited input. He shared a copy of a review on the progress on the NVP last year, indicating that 

a few hardcopies were published. Angela Shen has returned to NVPO after a stint at the United 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

19 

States Agency for International Development (USAID). Among other efforts, Ms. Shen will head 

NVPO’s adult immunization efforts. 

Introduction

Dr. José R Romero

Chair, Child and Adolescent Immunization Work Group

Dr. Romero introduced this session on behalf of Child and Adolescent Immunization WG. He 

reminded everyone that the schedule is presented for vote every fall, given that the ACIP’s 

approval is necessary prior to publication of the schedule in January or February of the following 

year. ACIP’s approval is also necessary before its partners, the American Academy of 

Pediatrics (AAP), American Academy of Family Physicians (AAFP), and American Congress of 

Obstetricians and Gynecologists (ACOG) review and approve the schedule. No new policy is 

established by the schedule; rather, it reflects a summary of published ACIP recommendations. 

These edits are intended to improve the readability and utility of the schedule, and hence 

translate the respective ACIP recommendations into language that is easy to interpret for the 

busy provider.

This year, only a few of the vaccines on the schedule required attention. The proposed 

schedule and the full set of footnotes are posted on the ACIP members’ background website. 

The most significant changes are in Figure 1, which is a reconfiguration of the order in which the 

vaccines are presented. They are listed in order from earliest to latest administration. In 

addition, meningococcal B vaccine (MenB) vaccine has been added to the figure and the 

footnotes. Also, clarifications were made to diphtheria, tetanus, acellular pertussis (DTaP), 

polio, and human papillomavirus (HPV). 

Child and Adolescent Immunization Schedule 2015

Candice L. Robinson, MD, MPH

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention

Dr. Robinson indicated that there were proposed changes for Figures 1 and 2, as well as the 

footnotes. On the cover page, only the year was changed. Proposed Figure 1 changes for the 

2016 schedule include the following:

 A purple bar, which represents the range of recommended ages for certain high-risk groups, 

has been added to Hib line and extends from 5 years through 18 years. This was added to 

correspond with text in the footnotes and published recommendation for administration of 

Hib in this age group for unvaccinated persons with high-risk conditions.

 In the 2015 schedule, this bar (half green/half purple bar) within the Hep A line was 

represented in the key below figure 2. However, since each color is already present in the 

key, this bar has been removed from the key in the proposed 2016 figure.

Child and Adolescent Immunization Schedule

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

20 

 The Tdap line has been moved down, given a desire to have the vaccines routinely 

recommended by age group (gold bars) aligned from the earliest age (hepatitis B) to older 

ages (Tdap, HPV, and meningococcal vaccines in adolescence).

 The HPV nomenclature will be changed to reflect the new HPV nomenclature format. For 

example, HPV4 is now referred to as 4vHPV.

 In the HPV line, a purple bar has been added from age 9 through 10 years, for children at 

high-risk due to history of sexual abuse. This is in line with currently published HPV 

guidelines. Additional information has been added to the footnotes which will be discussed 

later.

 A line for meningococcal B vaccine has been added to the schedule, with both a purple bar 

denoting high risk vaccination beginning at age 10 years, and a blue bar beginning at 16 

years denoting non-high risk groups that may receive this vaccine, subject to individual 

clinical decision making. The blue bar is appropriate here given that the recommended 

ages for permissive use of meningococcal B vaccine is between 16 and 18 years.

 The pneumococcal polysaccharide bar has been moved to the bottom of the figure, because 

this vaccine is not routinely recommended for any population.

This is the resulting proposed figure 1:

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

21 

There is a minor proposed change for Figure 2, the catch-up schedule. In the Tdap line, the 

dose 2 to dose 3 column, Tdap/Td was added to the list of possible previous vaccines: 

 

Proposed changes within the footnotes include the following:

 The Red Book reference in the additional information section has been updated to the 30th

edition.

 Footnote 3, the DTaP vaccine footnotes, has been revised to add Quadracel® to the 

minimum age exception line. The instructions were clarified regarding administration of an 

inadvertent dose of DTaP. It now reads “If the fourth dose of DTaP was administered at 

least 4 months, but less than 6 months, after the third dose of DTaP, it need not be 

repeated. The 4-day grace period may not be used for a fourth dose given less than 6 

months after the third dose of DTaP”. The description of “inadvertent dose” was used to 

indicate that this shortened interval between doses should not be used prospectively; 

however, the dose could be counted as valid after the fact.

 For footnote 7, inactivated polio, in response to questions from providers, guidance was 

added for inactivated polio vaccine (IPV) use in patients who have previously only received 

oral polio vaccine (OPV), and did not receive any doses after their 4th birthday. The addition 

reads “If only OPV were administered, and all doses were given prior to 4 years of age, one 

dose of IPV should be given at 4 years or older, at least 4 weeks after the last OPV dose.” 

This is consistent with guidance provided by the SMEs. 

 In the influenza footnote, the MMWR references were updated to those for the 2015-2016 

influenza season. No other changes have been made to this footnote.

 HPV vaccination recommendations now include the 9-valent HPV vaccine, in addition to the 

bivalent and quadrivalent HPV vaccines. The footnote also contains the nomenclature

change for HPV vaccines. The intervals between vaccine doses were clarified by 

restructuring the sentence without adding to or deleting any of the previous words. Text was 

also added regarding HPV vaccine use in high-risk children to correspond with the added 

purple bar discussed earlier. It reads “Administer HPV vaccination beginning at age 9 years 

to children and youth with any history of sexual abuse or assault who have not initiated or 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

22 

completed the 3-dose series.” This recommendation is part of the already published HPV 

guidelines.

 For the Meningococcal vaccines, the following revisions were made:

 The word “conjugate” has been removed from the footnote title and the 

meningococcal B vaccines have been added.

 

 Guidance regarding administration on meningococcal B vaccine has been added to 

the routine vaccination section.

 A new “Clinical Discretion” section has been added with instructions for MenB 

administration that read “Young adults aged 16 through 23 years (preferred age 

range is 16 through 18 years) may be vaccinated with either a 2-dose series of 

Bexsero® or a 3-dose series of Trumenba® vaccine to provide short-term protection 

against most strains of serogroup B meningococcal disease. The two MenB 

vaccines are not interchangeable; the same vaccine product must be used for all 

doses.”

 Within the “Vaccination of persons with high-risk conditions” section, guidance for the 

administration of Bexsero® and Trumenba® as well as the schedule has been added. 

It reads “Persons 10 years or older who have not received a complete series: 

Administer either a 2-dose series of Bexsero®, at least 1 month apart or a 3-dose 

series of Trumenba®, with the second dose at least 2 months after the first and the 

third dose at least 6 months after the first. The two MenB vaccines are not 

interchangeable; the same vaccine product must be used for all doses.”

 Clarification was added on what constitutes a persistent complement component 

deficiency.

 For both sections, separate subsections were added for meningococcal conjugate 

vaccines and meningococcal b vaccines.

 The MenB vaccines Bexsero® and Trumenba® were added to the list of 

meningococcal vaccines to administer or complete an age- and formulationappropriate series during community outbreaks attributable to the vaccine serogroup.

 The MenB vaccine policy note reference and associated web address will be added 

when available. 

The WG will make revisions as necessary based on feedback from ACIP and CDC internal 

clearance. A cleared, edited copy will be submitted to AAP, AAFP, and ACOG by January 1, 

2016. The final edited copy will be sent to partner organizations for preparation of publication in 

their journals or their on-line publications by January 2016. Publication on the CDC website will 

occur in January to February 2016. Dr. Robinson thanked all of the CDC SMEs for their support

and endless patience with the rewrites. 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

23 

Discussion Points

Dr. Kempe noted that 9vHPV vaccine did not appear to have been added to Figure 1.

Dr. Robinson indicated that it would be corrected before publication.

Dr. Walter noted that the DTaP vaccine grace period was mentioned only on the note and at the 

top of the schedule. It might be helpful to reference back to the top of the schedule for the 

reader who might just be reading for that particular vaccine.

Dr. Robinson replied that she would make a note of this.

Referring to the second footnote slide, Dr. Sawyer said he did not understand why the 4-day 

grace period needed to be referenced because it already said “if the vaccine is given more than 

4 months after the previous dose, it need not be repeated.” It was unclear to him how the grace 

period comment added additional information.

Dr. Robinson said they could clarify that the grace period would not relate to the 4 months. If it 

is given at 4 months, there is no 4-day grace period. That could be made clearer or be omitted 

in the future.

Since there is typically a 4-day grace period before 6 months and here it was say 2-month grace 

period in terms of an inadvertent dose given up to two months before it was due, Dr. Moore

suggested that there was no need to re-reference an additional grace period. It should simple 

say if a dose is given up to 2 months early inadvertently, it does not have to be repeated. That 

is the grace period for that particular dose.

Dr. Walter concurred that this is very confusing to the reader.

Dr. Robinson agreed that the 4-day grace period line could be removed.

Regarding the blue bar for MenB vaccine, which meant a Category B recommendation for 

clinical decision-making, Dr. Harriman expressed concern that this might make it seem like a 

lesser recommendation to providers.

Dr. Messonier said this marked the first time that they had tried to portray on the infant schedule 

the idea of a permissive recommendation. They must move forward with the schedule due to 

the time limit, but CDC will commit to a more comprehensive assessment of these schedules 

and how providers interpret them. The primary audience is providers, and as more vaccines 

have been added, the schedule has become highly complicated. It is a good time to review it 

and consider how to take advantage of modern technology. Part of that assessment will be 

making sure that people understand the various bars and what they mean.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

24 

Vote: Child and Adolescent Immunization Schedule

Dr. Rubin made a motion to approve the Child and Adolescent Immunization Schedule. Dr. 

Romero seconded the motion. The motion carried with 15 affirmative votes, 0 negative votes, 

and 0 abstentions. The disposition of the vote was as follows:

15 Favored: Bennett, Belongia, Ezeanolue, Harriman, Harrison, Karron, Kempe, Moore, 

Pellegrini, Romero, Reingold, Riley, Rubin, Stephens, Walter

 0 Opposed: N/A

 0 Abstained: N/A 

Introduction

Harriman, Kathleen, PhD, MPH, RN 

Chair, Adult Immunization Work Group

Dr. Harriman reminded everyone that ACIP updates the adult immunization schedule each year. 

The schedule represents current ACIP policy and also updates approved policy changes from 

ACIP meetings. The Adult Immunization WG meets monthly and engages in ongoing 

consultation with vaccine SMEs to recognize changes over time. Updates in adult immunization 

schedule are approved by the following:

 American College of Physicians (ACP) 

 American Academy of Family Physicians (AAFP) 

 American Congress of Obstetricians and Gynecologists (ACOG) 

 American College of Nurse Midwives (ACNM) 

The adult immunization schedule is published in the MMWR and the Annals of Internal 

Medicine.

The 2016 adult immunization schedule updates are primarily based on 2015 updates in HPV, 

meningococcal, and pneumococcal vaccine recommendations. They reflect the ACIP policy 

changes associated with the recommended use of 9-valent HPV vaccine, serogroup B 

meningococcal vaccines, and the intervals between 13-valent pneumococcal conjugate 

(PCV13) and 23-valent pneumococcal polysaccharide (PPSV23) vaccines. 

Adult Immunization Schedule 2015

Dr. David Kim

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention

In this presentation, Dr. Kim described the proposed changes to the 2016 adult immunization 

schedule. HPV vaccine recommendations now include three vaccines for females (2vHPV, 

4vHPV, 9vHPV) and two vaccines for males (4vHPV, 9vHPV). There has been a nomenclature 

Adult Immunization Schedule

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

25 

change for HPV vaccines. For example, HPV4 is now referred to as 4vHPV. Females aged 19

through 26 years are routinely recommended to have a 3-dose series of 2vHPV, 4vHPV, or 

9vHPV unless they have been vaccinated previously. Males aged 19 through 21 years are 

routinely recommended to have a 3-dose series of 4vHPV or 9vHPV unless they have been 

vaccinated previously. Men who have sex with men (MSM) and immunocompromised persons, 

including those with HIV infection, are recommended to have a 3-dose series of 4vHPV or 

9vHPV through age 26 years if not vaccinated previously. The 2016 adult immunization 

schedule also contains a minor word change with the generic term “HPV vaccination” replacing

specific HPV vaccine types.

The 2016 adult immunization schedule contains updates in the intervals between PCV13 and 

PPSV23. For immunocompetent adults ≥65 years, PPSV23 should be given at least 1 year

following PCV13. The “at least 1-year interval” in the 2016 schedule replaces the “6 to 12 

months interval” in the 2015 schedule. Note that the interval from PCV13 to PPSV23 is now the 

same as the interval from PPSV23 to PCV13. Also worth noting is that in February 2015, CMS 

implemented revised regulations for pneumococcal vaccines that allow for Medicare coverage 

for the different second pneumococcal vaccine 1 year after the first vaccine. The change in the 

ACIP-recommended interval between PCV13 and PPSV23 makes ACIP recommendations 

consistent with the current Medicare policy. The 2016 schedule also corrects two errata

contained in the 2015 schedule, which are as follows:

 “Adults aged ≥19 years” replaces “adults aged 19 through 64 years” as was in the Policy 

Note for pneumococcal vaccination of adults with immunocompromising conditions, 

functional or anatomical asplenia, CSF leaks, or cochlear implants

 “Adults aged 19 through 64 years who smoke cigarettes or reside in nursing homes or 

long-term care facilities: 

 “Adults aged 19 through 64 years who... reside in nursing home” is removed 

from the group of adults routinely recommended to receive PPSV23; these adults 

“should be assessed for PPSV23” 

 “Adults aged 19 through 64 years who smoke cigarettes” remains an indication 

for PPSV23

During the June 2015 ACIP meeting, recommendations for the use of MenB vaccination were 

made. As shown in the 2016 adult immunization schedule, MenB vaccination is featured 

separately from the quadrivalent meningococcal conjugate vaccine (MenACWY) and 

meningococcal polysaccharide vaccine (MPSV4). A 2-dose series of MenB-4C (Bexsero®) or a 

3-dose series MenB-FHbp (Trumenba®) is recommended for adults with anatomical or 

functional asplenia, persistent complement component deficiencies, microbiologists who are 

routinely exposed to isolates of Neisseria meningitides, and those at risk because of 

meningococcal disease outbreaks attributable to serogroup B. MenB vaccination is not 

recommended for persons who travel or live in countries in which meningococcal disease is 

hyperendemic or epidemic, because meningococcal disease in these countries is generally not 

caused by serogroup B. The MenB recommendation for adults with asplenia and complement 

deficiencies is represented in yellow on the schedule, meaning that it is recommended. It is 

represented in purple for all other listed indications, which means it is recommended if another 

risk factor is present.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

26 

Young adults 16 through 23 years, with a preferred age range of 16 through 18 years, may be 

vaccinated with a MenB vaccine series to provide short-term protection against most strains of 

MenB disease. This Category B recommendation for MenB vaccination has not been fully laid 

out in the 2016 adult immunization schedule as there are issues that remain to be resolved, 

such as how to best align the new Category B recommendation with existing recommendations 

that may also be considered permissive. An example might be the recommendation that 

hepatitis A vaccine can be administered to any person seeking protection. The Adult 

Immunization WG plans to conduct focus group and other human factors testing to determine 

how to best present this information. In the interim, the WG proposes that the Category B 

recommendation for MenB vaccination for adults aged 19 through 23 be presented in the 

schedule footnotes but not included in the figures. 

There are additional changes in the footnotes for meningococcal vaccination. One change was 

to add MenB to the statement on HIV to read, “HIV infection is not an indication for routine 

vaccination with MenACWY or MenB vaccine.” Two additional pieces of notable information

have been added. The first is that “MenB-4C or MenB-FHbp vaccine may be administered 

concomitantly with MenACWY vaccine, but at a different anatomic site if feasible” and the 

second is that “the two MenB vaccines are not interchangeable; the same vaccine product must 

be used for all doses.” Finally, MenB vaccine has been added to the Contraindications and 

Precautions Table with the same information as MenACWY:

 Contraindications: Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to 

a vaccine component

 Precautions: Moderate or severe acute illness with or without fever

The proposed changes to Figure 1 of the draft 2016 adult schedule include the following:

 For Tdap, the text in the yellow bar that formerly stated “substitute 1-time dose of Tdap 

for a Td booster” has been simplified to state “substitute Tdap for Td once”

 For measles, mumps, and rubella (MMR), the text in the yellow bar stating “1 or 2 doses” 

has been clarified to “1 or 2 doses depending on indication”

 For PCV13, the text “1-time dose” that straddles the purple and yellow segments of the 

bar has been changed to “1 dose,” similar to zoster vaccination, so that it does not 

confuse the reader into thinking that PCV13 is the only once-in-a-lifetime vaccine

 The text for PPSV23 for adults younger than 65 years of age has been modified from “1 

or 2 doses” to “1 or 2 doses depending on indication”

 The text for Hepatitis A has been changed from “2 doses” to “2 or 3 doses depending on 

vaccine” to account for hepatitis A and B combination vaccine that is administered in a 3-

dose series

 Meningococcal has been moved to below Hepatitis B and now appears in two rows, one 

for MenACWY/MPSV4 and another for MenB; both vaccines have purple bars running 

across all age groups

 The text for MenACWY/MPSV4 states “1 or more doses depending on indication”

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

27 

 The text for MenB states “2 or 3 doses depending on vaccine” to account for the two 

MenB vaccines with different dosing schedules

 The text in the purple bar for Haemophilus influenzae type b (Hib) was changed from “1 

or 3 doses” to “1 or 3 doses depending on indication”; more on this in Figure 2

 The language in the legend for the yellow bar “recommended for all persons” and the 

purple bar “recommended for persons with a risk factor” has been modified slightly for 

consistency; the inclusion of age in the purple legend in Figure 1 may be redundant 

because Figure 1 lists recommendations by age groups, but it is needed in Figure 2 in 

which recommendations are organized by indication

The proposed changes to Figure 2 of the draft 2016 adult schedule include the following:

 Some of the changes in Figure 2 are the same as for Figure 1

 The text in the indication bar across the top for immunocompromising conditions and 

HIV infection has been simplified

 The segmented yellow boxes and the text that specifies which types of influenza vaccine 

can be administered for specific indications have been condensed to a single yellow bar 

containing the text “1 dose annually” across all indications; this simplification is 

consistent with the ACIP recommendation that all persons 6 months of age and older 

receive the influenza vaccine 

 For PPSV23, the text “1 or 2 doses” has been changed to “1, 2, or 3 doses depending 

on indication” to reflect that the maximum number of doses of PPSV23 that an adult 

should receive is 3; that is, 2 for an immunocompromising condition and 1 for reaching 

the age of 65

 As in Figure 1, the former single row for meningococcal vaccine is now two rows for 

MenACWY/MPSV4 and MenB

 The text for MenACWY/MPSV4 and Men B are the same as in Figure 1 but the text 

straddles the purple and yellow bars for Figure 2; the yellow reflects the 

recommendation for MenACWY and MenB for adults with asplenia and complement 

deficiencies

 MenB in pregnancy has been left white or blank, indicating that there is no 

recommendation for MenB vaccination during pregnancy

 For Hib, the 2015 text “1 or 3 doses” has been changed to state “3 doses posthematopoietic stem cell transplantation (HSCT) recipients only” for the 

immunocompromising conditions column and “1 dose” for other conditions for which Hib 

vaccine is indicated

 “Contraindicated” was added, shown as a red box in the legend 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

28 

Here are the drafts of proposed Figures 1 and 2 reflecting the changes as described for the 

2016 adult immunization schedule:

 

Based on the discussion and recommendations by ACIP during this session, the draft 2016 

adult immunization schedule will be revised and reviewed again by the WG and SMEs. 

Concurrence will then be obtained by the ACP, AAFP, ACOG, and ACNM. The revised adult 

immunization schedule, including figures and footnotes, will be submitted to CDC for clearance. 

The cleared adult immunization schedule will be submitted to the MMWR as a Notice to the 

Reader referring the reader to the CDC website to access the updated schedule, and published 

in the Annals of Internal Medicine in February 2016. 

Discussion Points

Ms. Pellegrini recalled that when the MenB blue bar was added, there was discussion about 

coordinating with the adult schedule to carry the blue bar up to age 23 since the age 

recommendation straddles both schedules.

Dr. Romero replied that this was discussed originally, but then he and Dr. Strikas met with the 

group and decided to leave that off until further discussion.

Given the complexity of the schedule and the layout, Dr. Riley thought this was probably the 

best they could do. However, she emphasized how difficult it is to follow the columns. The 

MenB issue and the blue line highlight the confusion. If the schedules do not pair up, it makes it 

more confusing. There is no way to know currently if a 22 year old woman with no issues 

presents to a physician and asks for a MenB vaccine, just looking at the adult schedule and not 

reading the footnotes (which are blurry and too small to read), the assumption may be that the 

vaccine is unsafe. Her concern is that when information is not clearly laid out, there is a natural 

assumption that a vaccine is unsafe, cannot be given, or should not be given. This is the same 

comment for pregnancy in terms of understanding what can be given, what should be given, 

and what cannot be given.

Dr. Kempe shared Dr. Riley’s concerns. At a minimum, the child and adult schedules should 

pair up. The decision for how to portray the blue bar for each should be the same. Realizing 

that they just voted on the childhood schedule, making a different decision for the adult 

schedule did not make sense to her. Family medicine will be looking at both schedules.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

29 

Dr. Bennett thought the problem was that the pediatric and adult schedules do not pair up in 

many ways. In addition, the adult schedule is difficult for providers because there is much 

information in the footnotes that is not in the schedule itself. The goal must be to develop an 

adult schedule that is more analogous to the pediatric schedule. That is more of an issue than 

presence or absence of the blue bar.

In reviewing the footnotes, Dr. Walter noted that “3 doses” referred only to 2vHPV and 4vHPV 

and not 9vHPV.

Dr. Stephens agreed that while it was routinely true that MenB need not be recommended for 

travelers, there are issues and settings in which group B outbreaks do occur. New Zealand is 

an example of that. “MenB is not routinely recommended for travelers” may be a better 

statement than “not recommended for travelers.”

Dr. Fryhofer (AMA/ACP) expressed her gratitude for the time and effort that went into making a 

very difficult schedule somewhat more understandable through the graphics. Regarding 

footnote 8 for pneumococcal vaccination, it was not clear for those 65 and older who are 

immunocompetent and who are high risk because they have cochlear implants or a 

cerebrospinal fluid leak (CSF) leak whether the interval is 8 weeks or 1 year. Based on the two 

published recommendations that are posted on the ACIP website from October 12, 2012 and 

September 4, 2015 with the intervals, it appeared to her that for anyone age 19 and older who is

immunocompetent, the interval would be 8 weeks.

Dr. Kim replied that for those who are immunocompromised who are 19 through 64 years of age 

and 65 years of age and older, the interval would be 8 weeks. For immunocompetent adults 65 

years of age and older, the interval is 1 year. The interval is 8 weeks for immunocompetent 

adults 65 years of age and older who have cochlear implants or CSF leak.

Dr. Fryhofer (AMA/ACP) emphasized that the interval of 8 weeks for immunocompetent adults 

65 years of age and older who have cochlear implants or a CSF leak needs to be reflected in 

the footnotes.

Vote: Adult Immunization Schedule

Dr. Reingold made a motion to approve the Adult Immunization Schedule. Dr. Rubin seconded 

the motion. The motion carried with 15 affirmative votes, 0 negative votes, and 0 abstentions. 

The disposition of the vote was as follows:

15 Favored: Bennett, Belongia, Ezeanolue, Harriman, Harrison, Karron, Kempe, Moore, 

Pellegrini, Romero, Reingold, Riley, Rubin, Stephens, Walter

 0 Opposed: N/A

 0 Abstained: N/A 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

30 

Introduction

Lorry Rubin, MD

Chair, Meningococcal Work Group

Advisory Committee on Immunization Practices

Dr. Rubin reminded everyone that the following ACIP recommendation for use of serogroup B 

meningococcal vaccines in adolescents and young adults was voted on during the June 2015 

ACIP meeting, for which a Policy Note is scheduled to be published in the MMWR on October 

23, 2015:

“A serogroup B meningococcal (MenB) vaccine series may be administered to 

adolescents and young adults 16 through 23 years of age to provide short term 

protection against most strains of serogroup B meningococcal disease. The preferred 

age for MenB vaccination is 16 through 18 years of age. (Category B)”

The WG recognizes that there are ongoing challenges when considering routine use of MenB 

vaccines in adolescents. As a reminder, the proportion of serogroup B cases that could be 

prevented with MenB vaccines is unknown. The breadth of strain coverage is estimated, with 

actual breadth of strain coverage unclear. Available antibody persistence data suggests that 

there is limited duration of protection. Effectiveness data are not available, and licensure was 

based on bactericidal activity. Universal programs have not been implemented in any country to 

date. The impact on carriage is unknown, as is the potential impact of vaccine pressure on 

circulating strains.

Additional data for MenB vaccines that have been reviewed by the WG since June 2015 include 

some preliminary safety and immunogenicity data from two Phase 3 studies for the MenB-FHbp 

vaccine, including immunogenicity data on 10 secondary strains. Pfizer plans to present these 

data to ACIP in February 2016. The WG also reviewed an additional safety summary received 

from CDC’s Immunization Safety Office (ISO). Relatively few reports have been received on 

MenB-FHbp (n=65) and MenB-4c (n=21) through the Vaccine Adverse Event Reporting System 

(VAERS) as of October 5, 2015. No safety signals have been detected to date. Few doses 

have been administered to the Vaccine Safety Datalink (VSD) population to date. Safety 

assessment can begin when a larger number of doses have been administered and data 

accumulated.

An ad hoc WG comprised of ACIP Meningococcal WG members, ACIP members, state public 

health officials, college health professionals, and CDC reconvened on September 3, 2015 with 

biweekly meetings. The objectives of this ad hoc WG are to: 1) review available data on the 

recent epidemiology of meningococcal disease and outbreaks; 2) review safety and 

immunogenicity of meningococcal vaccines; and 3) update and harmonize the current 

meningococcal outbreak guidelines for serogroups A, B, C, W, and Y. The Meningococcal 

Outbreak WG recommendations will be presented in an informational session during the 

Meningococcal Vaccines

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

31 

February 2016 or June 2016 ACIP meeting. Harmonized outbreak guidelines eventually will be 

published in the MMWR. 

Immediate future Meningococcal WG activities are to reevaluate the policy options for use of 

MenACWY in MSM or HIV-infected MSM. This will include review of prior ACIP discussions 

which took place in February 2014; and evaluating recent data on outbreaks of serogroup C 

meningococcal disease occurring in MSM and sporadic cases, including results of an analysis 

to estimate risk for meningococcal disease among MSM.

The topic of today’s session is a presentation regarding a serogroup C outbreak among MSM in 

Chicago in 2015.

Serogroup C Outbreak Among MSM, Chicago 2015

Sarah Kemble, MD

Chicago Department of Public Health

Dr. Kemble shared the Chicago Department of Public Health’s (CDPH’s) experience with a 

serogroup C meningococcal disease outbreak among Chicago-area MSM in 2015. She began 

by reviewing the epidemiology of the invasive meningococcal disease outbreak that occurred in 

the Chicago metropolitan area during the summer of 2015, and CDPH’s response to the 

outbreak as it evolved. She also shared some details of CDPH’s vaccination campaign, and 

discussed some of the challenges encountered in implementing the campaign and estimates of 

its cost.

CDPH became aware of the first case in this outbreak in mid-May. The case occurred in an 

HIV+ male who on initial interview reported being in a monogamous relationship with another 

male. There were a limited number of contacts, therefore, who required chemoprophylaxis. At 

that point, this seemed to be a single case. However, within two weeks, two additional cases 

were reported among MSM. At that point, CDPH became aware that an outbreak was likely 

occurring. They were not yet aware of the serogroup status of these cases, but when they were 

confirmed on June 2, 2015, a vaccination campaign was implemented on June 3, 2015. Press 

releases, an Epidemic Information Exchange (Epi-X), and a Health Alert Network (HAN) alerts 

were issued to local clinical partners to issue vaccination recommendations. The initial 

vaccination recommendations issued on June 3rd were focused on high-risk groups as defined 

by the epidemiology of the initial 3 cases of which the CDPH was aware. This meant HIV+ 

MSM, MSM regardless of HIV status who had close or intimate contact with anonymous 

partners, and those who sought sexual partners through use of on-line hook-up apps. On the 

day the recommendations were issued, a fourth case had illness onset and was reported to 

CDPH within the subsequent couple of days. Two additional cases occurred in the subsequent 

two weeks.

At this point, CDPH was dealing with 6 cases of invasive meningococcal disease (IMD) of the 

same serogroup occurring within a limited geographic area over a very short period of time. 

They knew that the ACIP-recommended threshold for initiation of a meningococcal vaccination 

campaign was an incidence of 10/100,000 among the at-risk population. ACIP guidelines also 

recommended consideration for a campaign when multiple cases occur within a short period of 

time, or when cases occur within a shared institution or in close geographic proximity. The 

initial recommendation for vaccination of HIV+ and high-risk MSM was based on the estimate 

that IMD incidence among Chicago HIV+ MSM had reached 19/100,000 as of June 3rd, well 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

32 

exceeding the ACIP threshold. However, a number of challenges were encountered in 

implementing a vaccination campaign targeted at these more narrowly defined groups. The 

stigma associated with diagnosis of HIV and with admitting to anonymous sex and use of “hookup” apps to identify sex partners complicated the vaccination message and limited vaccine 

acceptance. This was particularly a problem in the black community, which was a concern 

because the majority of cases were occurring among black MSM. CDPH reconsidered the 

recommendations as the case numbers continued to grow. They estimated that IMD incidence 

among all Chicago MSM regardless of HIV status had reached 10/100,000 as of June 18th, 

when the 6th case was also confirmed to be serogroup C [Bilukha OO, National Center for 

Infectious Diseases, Centers for Disease Control and Prevention. Prevention and control of 

meningococcal disease: recommendations of the Advisory Committee on Immunization 

Practices (ACIP). MMWR RecommRep 2005;54:1-21]. This was reaching a threshold that 

would define an outbreak more broadly in the MSM population in Chicago.

Consideration was also given to upcoming festivals and events that occur during the summers 

in Chicago, such as Pride Week and Black Pride. Many of the cases were of this demographic. 

This presented a risk for greater/broader transmission in the MSM population in Chicago, and 

for visitors from other states and countries. It also represented an opportunity to get vaccine 

out. With all of this in mind, CDPH issued expanded vaccination recommendation to all Chicago 

MSM as of June 18th. This was the day on which the 6th case was confirmed to be serogroup C. 

Following that expanded recommendation, one additional case was reported in the Chicago 

area at the end of June. Thankfully since then, no additional cases have been reported.

In summary of the case characteristics, 7 cases of serogroup C IMD were identified during this 

outbreak (6 in Chicago and 1 in a neighboring county). The age range of cases was from 29 to 

54 years. One case was fatal. Of the 7 cases, 6 were African American and 5 were HIV+. CD4 

counts of those for whom information was available ranged from 91 to 960. Only one case had 

a CD4 count less than 200, and the fatal case had the highest CD4 count of 960. Of the cases, 

5 reported anonymous sex, including 1 sex worker, and 5 cases reported meeting partners 

using “hook-up” apps. 

Extended case investigations were performed for all cases in this outbreak, meaning an attempt 

was made to trace all intimate contacts of cases going back 90 days prior to illness onset, by 

referencing the CDPH sexually transmitted infection (STI) partner services database and 

through in-person case interviews when possible. The primary goal of contact tracing was to 

make appropriate recommendations for chemoprophylaxis. Up to 9 contacts and a median of 4 

contacts per case met indications for prophylaxis. Close or intimate contact with the case within 

14 days of illness onset was considered to be an indication for chemoprophylaxis. 

One goal of the extended investigations was to attempt to identify direct epidemiologic links 

between outbreak cases. This proved challenging because many contacts were anonymous or 

used aliases or temporary phone numbers. No direct epidemiologic links between cases were 

found; however, the extended investigations did serve some other important functions such as 

allowing CDPH to provide HIV partner services or to identify additional vaccination targets in the 

form of individual contacts, more extended friend networks, or venues frequented by cases and 

their social networks. For example, some cases agreed to post a message on their Facebook 

page urging other MSM in their friend networks to get vaccinated against meningitis. It was also 

through case interviews that several gyms were identified as being key venues for reaching 

African American MSM.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

33 

Laboratory testing performed at CDC revealed that all 7 Chicago-area case isolates shared an 

indistinguishable pulsed-field gel electrophoresis (PFGE) pattern and multi-locus sequence type 

(MLST). The isolates also had less than 12 single nucleotide polymorphism (SNP) differences 

by whole genome sequencing (WGS), meaning that they were also indistinguishable by this 

method. Approximately two weeks after the last case was reported in the Chicago area, a case 

was reported in Minnesota that was closely related by laboratory testing. Again, no direct 

epidemiologic links were found between this and the Chicago-area cases; however, concern 

that it could be related due to similar risk factors (HIV+ status and high-risk behaviors), in 

conjunction with Minnesota, CDPH issued an Epi-X that included a call for cases and reporting 

of MSM status for all meningococcal disease cases. Review of Chicago’s meningococcal 

disease epidemiology over the past few years showed that since 2013 when Chicago has been 

more regularly tracking MSM status, the vast majority of Chicago’s cases have been among 

MSM.

In terms of the CDPH meningococcal vaccination campaign components, the campaign began 

with federally funded 317 vaccine distribution. This was done through CDPH “pop-up” clinics, 

partner clinic sites, and pharmacies. Walgreens was a major partner with CDPH in these 

efforts. There was a communications and media component to the campaign, as well as 

community outreach through Ryan White grant recipients and other community partners. In 

terms of evaluation, CDPH attempted to track how it was doing as the response unfolded. The 

festival events were used as opportunities to establish pop-up clinics where vaccine could be 

offered in a mass-vaccination setting where people were already congregating. This was 

additionally folded into some of the “back to school” vaccination efforts as the summer wore on, 

and there were some broader community events that were brought to CDPH by community 

partners, at which vaccination staff and vaccine were provided. All of the pop-up clinic events 

and permanent clinic sites were mapped, and an interactive map was provided that could be 

accessed by the CDPH website so that people could identify locations where they could get 

vaccinated, as shown in the following illustration:

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

34 

The media campaign included a standard press release to television, radio, and print media. 

Paper canvassing included posters, flyers, and palm cards. There were also billboards, Action 

Alerts to community partners, Twitter feeds, Facebook posts, push notifications on hook-up 

apps, and digital advertisements on Facebook, Twitter, and Google. CDPH engaged a number 

of community-based partner organizations, including HIV/MSM providers; STI clinics; nonclinical community-based organizations (CBOs); Lesbian, Gay, Bisexual, and Transgender 

(LGBT) Aldermen’s Caucus; African American Aldermen’s Caucus; gyms; bars/clubs; health 

fairs; community events; and House Ball networks. The House Ball network is a social 

phenomenon among black gay men in Chicago. This is akin to a fraternity system, which 

provides mentorship to young black men who are coming out and may not have role models 

and is like an alternate family structure. They have a number of parties as well monthly, 

throughout the summer, and throughout the year so this was an opportunity to work with some 

of those groups to incorporate the vaccination messages and possibly provide vaccine at some 

of their events.

 

Evaluation was primarily through reports back to CDPH from partners that received 317 

vaccine, which are shown by week and site in the following graph:

The green bars represent CDPH-administered doses at pop-up clinic sites, the dark blue bars 

represent one of CDPH’s highest volume clinical partners (Howard Brown Health Center), the 

red bars represent CDPH’s other highest volume clinical partner (Core Center), and the purple 

bars represent Walgreens. There are some issues with reporting lags, so the large jump in the 

middle with the dark blue bars is primarily reporting lag of vaccine that was probably given in the 

earliest weeks of the campaign by Howard Brown Health Center. Overall, the highest number 

of vaccine doses were given out early on due to Pride Week and associated events. This was 

the biggest yield time to get vaccine out. The turquoise bars represent the amalgamation of 

other clinical partners, and it has been those clinical partner sites that have continued to get 

vaccine doses out after the initial push.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

35 

A number of challenges were encountered during this outbreak. One of the first challenges was 

deciding who was at risk. It can be difficult to determine who the denominator actually is. Most 

of the cases reported higher risk activities, but some did not and some identified as being in 

monogamous relationships. Many people use apps, but do not necessarily act on the partners 

they find there. Therefore, it is not clear whether app usage in and of itself is a risk factor or if it 

is what people do with the contacts they make through such apps. This is not a population who 

is stepping forward to indicate that they need to be vaccinated. Trying to find people who need 

to be vaccinated differs from a university setting in which there is a roster of students who 

belong to the university. One of the major challenges of this campaign pertained to 

demographics and disparities in access to care. The map on the left shows the prevalence of 

HIV among Black and Hispanic MSM in Chicago as of the end of 2014. The map on the right 

shows distribution of cases in the Chicago 2015 meningococcal outbreak by community area: 

Cases in the outbreak were distributed in areas of the city where prevalence of HIV among 

minority populations is known to be high. However, clinical and outreach resources are 

concentrated in the Northeast neighborhoods, with much more limited access for populations on 

the south and west sides.

This was complicated by the fact that Black MSM were the least aware of the outbreak, based 

on data by Dr. Temi Folaranmi, an Epidemic Intelligence Service (EIS) Officer who joined CDPH 

for an Epi-Aid during this outbreak. Thanks to Dr. Folaranmi, CDPH was able to collect a lot of 

data on vaccine acceptance and demographics of those who were at sites where vaccines were 

made available [Temi Folaranmi MD, MPH, MPP, EIS Officer, MVPD Branch, NCIRD, Centers 

for Disease Control and Prevention, Epi-Aid 6/2015–10/2015, Survey of Clients at Vaccination 

Sites].

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

36 

A number of community round table discussions were convened, particularly with Black MSM 

groups on the Southside and Westside, and some of the sentiment heard reflected the 

challenge of denial and stigma. Here are two examples of the comments made during the 

community round table discussions:

“When we first heard about this [outbreak] we assumed, it’s those white boys in Uptown 

bringing it in...We never thought it was happening in our community.”

“It feels like HIV all over again. Like, everything bad happens to [black gay men].”

 

Tracking vaccine administration was a challenge in and of itself. The highest risk groups were 

also the most difficult to reach, given that this includes Black gay men predominantly on the 

Southside and Westside of Chicago—the most underserved areas of Chicago. The nature of 

Pride Week and the festivals that occur is that they occur mostly on the Northeast side of the 

city, which is predominantly white and wealthier. The hope was that the demographic who 

needed to be reached would be attending these events. There are fewer opportunities on the 

Southside and Westside to get vaccine out in terms of festivals, events, and through standing 

clinics. Vaccine administration reported by site and area of town is shown in the following map:

Vaccine administration was also tracked by using the I-CARE vaccine registry and through 

several of the highest volume clinical sites that report into I-CARE. The initial weeks of the 

campaign showed most of the uptake in the Northeast corner of the city, again, the wealthier 

whiter areas. Over time, with the more targeted messaging developed and the work with 

community groups, uptake was increased in other areas of the city as well.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

37 

A preliminary assessment of the demographics of those who received vaccine reflected what 

would be expected based on the residential demographic distribution within Chicago, as shown 

in the following map:

CDPH felt confident that when they were vaccinating on the Southside, they were reaching 

much of the Black gay population.

There was also the challenge of HIV+ individuals requiring 2 doses of meningococcal vaccine 

given 8 weeks apart. A determination had to be made about how to identify those living with 

HIV, especially in a festival setting where it was not appropriate to ask people in front of others if 

they were HIV+. In addition, they had to ensure that those who were HIV+ returned for a 

second dose. Those challenges were met primarily by giving a generic message to all who 

approached the vaccination tables to let them know if they were HIV+, they would need a 

second dose.

In summary, the challenges encountered included how to reach members of social networks 

designed to preserve anonymity, how to facilitate communication and community participation to 

close knowledge gaps in underserved communities, and how to deliver vaccine in these areas 

despite the lack of infrastructure.

An effort is being made to estimate the cost of the campaign, which is in progress. Thus far, the 

total cost of the pop-up vaccine clinics is estimated to have been $51,672.76. This includes 

clinical staff (69%), outreach staff (20%), and medical supplies (11%). Virtually all of these 

clinics occurred during non-business hours, because that is when CDPH staff were available to 

vaccinate, and that is also when most of the events took place (e.g., weekends and after hours). 

The cost of vaccine is not included in this figure. The numbers of vaccines given by event type 

were not equal. Festivals had the highest yield in terms of the number of vaccines that could be 

administered with the fewest staff (n=2000), so the return on festival vaccinations was the 

highest. Bars were somewhat lower (N=607). Media costs are estimated to have been 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

38 

$19,000. This includes Facebook/Twitter ($15,000), Grindr ($1500), and Radio ($2500). Free 

media channels included Jack’d, Scruff, and Manhunt. Advertisements on the digital billboard 

system supported by the city were at no cost to CDPH. At this point, the total expenditure by 

DCPH in terms of money is estimated to have been $70,000 from May through October 2015. 

Staff time during work hours is estimated to have been 3700 person-hours, which amounts to 

466 8-hour work days. This is a significant opportunity cost to the health department in terms of 

not having time to work on some of its other usual activities.

In conclusion, the demographic most affected by the meningococcal outbreak in Chicago (e.g., 

African American, HIV+, and high-risk MSM) is also the most challenging demographic to reach. 

Pop-up clinics quickly boosted the numbers vaccinated, but permanent clinical sites were critical 

for a more sustained response. The vaccination campaign imposed a substantial burden on 

CDPH in terms of money and staff time.

Discussion Points

Dr. Harrison asked which vaccine CDPH used, whether WGS was done on the Minnesota case, 

and what the sequence type was.

Dr. Kemble replied that the vaccine provided through CDPH was Menactra®. The Walgreens 

sites predominantly gave Menactra®, but also used some private stocks and formulations. CDC 

performed WGS on the Minnesota case. It was closely related with greater than 99% similarity, 

but not less than a 12 SNP difference. It was more like a 74 to 84 SNP difference, but it was 

matched by PFGE; the PFGE sequence type was 428.

Dr. Stephens noted that there have been some reports of increased incidence of meningococcal 

urethritis among surveillance sites in the Midwest, and he wondered whether CDPH observed 

any increased reporting of meningococcal urethritis associated with the Chicago outbreak.

Dr. Kemble responded that CDPH was interested in this question because they were sharing 

the outbreak information with their clinical partners as it unfolded. Because of that, a couple of 

the partners brought cases to CDPH. Whether these were cases associated with the outbreak 

or just finders bias because they were talking about the outbreak was unclear, so two samples 

from these community clinical partners were sent to CDC. Neither of these samples could be 

typed and they were not matched by PFGE, so it is unlikely that they were related to the 

outbreak. However, it did raise the question of urethral carriage among these individuals and it 

would be interesting to see more data on that.

Dr. Duchin (NACCHO) asked what proportion of the vaccinated persons were in CDPH’s high 

risk target population among those who had disease, and whether an assessment was done to 

determine which of the multiple outreach efforts were successful in driving those in who did 

come to get vaccinated.

Dr. Kemble indicated that it was difficult to assess who was in the demographic CDPH thought 

was at highest risk because many people are not willing to share certain information, such as 

information about finding partners on hook-up apps. The first case initially reported being in a 

monogamous relationship, but on repeat interview once other cases were discovered it came 

out that there were two or three anonymous partners during the incubation period. Through the 

Epi-Aid, there was a survey that asked about some of these risk factors among people who 

attended vaccination events, many of whom did get vaccinated, but not all. About 40% of Black 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

39 

MSM reported use of apps, but there is likely to be underreporting. Data are lacking on HIV 

status because CDPH felt that asking people outright to share their HIV status when they came 

to get vaccinated would prevent people from coming to get vaccinated. The primary goal was to 

get vaccine out. The survey did ask about this, but not everyone chose to answer the question. 

She will review the survey data to determine what proportion reported being HIV+. It is certainly 

not as high for all-comers at these events as among the cases. In terms of which campaign 

components worked the best, looking at sheer numbers the festival events were the most 

successful. The subtext to that regards which events specifically reached Black MSM. That is 

the easiest component that could be assessed, other than parsing out risk factors. Some of the 

Ball Events and park events were the most successful at doing that, where most of the people 

vaccinated were Black MSM from the Southside or Westside. That was going into areas where 

they are known to hang out.

Dr. Gemmill (NACI) asked for the total number vaccinated in order to get an idea of cost per 

dose in this type of setting, whether only Chicago residents were immunized during events or if 

those from out of town were also included, and whether the vaccine campaign stopped the 

outbreak.

Dr. Kemble replied that the total number of vaccinated is not known because vaccination is 

ongoing with clinical partners providing vaccine. The current count is over 11,000 vaccinated 

and 15,000 doses distributed. With the reporting lag, the count will likely be 15,000 within the 

next couple of weeks. Immunization was not limited to Chicago residents. People were asked 

to fill in their address when they received the vaccine, but people were not told they could not 

get the vaccine if they were not from Chicago. About 9500 doses can be assessed through the 

I-CARE registry system, of whom 7500 provided a valid Chicago address. The rest is a 

combination of people who did not write down an address, wrote down a fake address, or were 

from other cities (a small number). A couple of thousand doses were administered between 

mid-June and the end of June when the last case was reported. It is difficult to know for certain 

whether the vaccination campaign stopped the outbreak, especially given that more of the 

highest risk demographic did not get vaccinated until somewhat later. Of course, CDPH hopes 

that this did stop the outbreak.

Dr. Reingold asked whether an attempt was made to try to ascertain risk factors for 

meningococcal disease in a case-control study in terms of sexual behaviors and so forth, and 

the extent to which CDPH worked with STI and HIV experts since this is a population with whom 

they work regularly. While it is true that there was a statistically significant relationship between 

awareness of the outbreak and race, all of these groups were about 80% to 90%, so he thought 

they achieved a pretty high level of awareness across the groups.

Dr. Kemble indicated that because the number of cases was so low, they did not pursue 

performing a case-control study. Risk factors were collected for all of the cases, but no attempt 

was made to assess controls and assess the same risk factors. That was done in New York 

City, and CDPH decided that their data were probably more valid given the numbers. Working 

with STI and HIV partners was brought to CDPH’s attention early on by CDC colleagues, and 

CDPH did reach out to its own STI division. That was a large part of the impetus to perform the 

extended case investigations and case interviews. This was done through a partnership with 

CDPH’s communicable disease staff who normally perform meningococcal investigations and 

an investigator from the STI-HIV division. Together, they conducted field visits and collected 

partner information from all of the cases. This was very helpful. Awareness was high among 

the younger demographic, but when parsed out to Black MSM below the age of 25, awareness 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

40 

was about 50%. The concern was that some of the highest risk group was still not as aware of 

the campaign as CDPH would have liked.

Dr. Whitely-Williams (NMA) noted that HIV counseling and testing experts already are targeting 

a very high risk population and are able to do the HIV testing. To combine awareness and 

vaccinating with that group of individuals would have been very helpful. By doing testing, 

counseling, and vaccinating through this mechanism it would avoid anyone having to disclose 

whether they were HIV+.

Dr. Kemble responded that they did try to partner with community-based Ryan White-funded 

organizations to conduct HIV counseling and testing along with meningococcal vaccination. It 

would have been great to compile that type of partner counseling data with the demographics of 

those vaccinated, but the logistics of it were too complicated in terms of space and organization 

to combine them that seamlessly—though it is a great idea.

Introduction

Ruth Karron, MD

Chair, Influenza Work Group

Dr. Karron reported that since the June 2015 ACIP meeting, the Influenza WG had considered 

the cost-effectiveness of high-dose versus standard-dose inactivated influenza vaccine (IIV) for 

persons ≥65 years, as well as clinical data for adjuvanted trivalent inactivated influenza vaccine 

(TIV). She indicated that during this session, the full ACIP membership would hear an update 

on influenza epidemiology and surveillance, and a report on the cost-effectiveness of high-dose 

versus standard-dose IIV for persons ≥65 years, and a report on the clinical data for adjuvanted 

TIV.

Epidemiology and Surveillance Update

Lynnette Brammer, MPH

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention

Ms. Brammer presented updates on international influenza activity, recent US influenza activity, 

and Southern Hemisphere vaccine recommendations. Based on an aggregation of influenza 

positives reported by the National Influenza Centres (NICs) in Southern Hemisphere countries, 

there was a mix of all viruses (H1N1pdm09, H3N2, A viruses not subtyped, B viruses). 

Information from individual countries reflects the variability observed in predominating viruses by 

countries, as illustrated by the following graphs of countries with recent activities:

Influenza

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

41 

The first two graphs on the top left are Australia and New Zealand, where there was a largely 

even distribution between H3N2 viruses and influenza B viruses. This is in contrast to what was 

observed in South Africa where there was predominantly H1N1pdm09 viruses, with some H3N2 

viruses and an uptick in influenza B late in their season. Recent activity in China has been 

predominantly H3N2. Bangladesh had a predominantly H1N1 season, although they have had 

an increase in H3N2 viruses more recently. In the Americas, Argentina had predominantly 

H3N2 viruses and very little B viruses. Their outbreak was sharp and brief. Brazil has a much 

more prolonged outbreak, which was H3N2 predominant with some influenza B virus at the end 

of their season. In contrast, Cuba has had a lot of H1N1 activity recently.

For the US, several changes have been made in how surveillance data will be reported for the 

coming season. Laboratory data have been obtained from the US World Health Organization 

(WHO) Collaborating Laboratories and the National Respiratory and Enteric Virus Surveillance 

System (NREVSS) laboratories, and data from clinical laboratories and data from public health 

have been split out and will be reported separately. Each of these components will be used to 

offer the best representation of the data. Regarding influenza positive data from US clinical 

laboratories from May 24, 2015 through October 10, 2015, influenza B was predominant in the 

late spring. As the summer progressed, influenza A became predominant. During the week 

ending October 10th, 1.2% of the specimens tested and reported to CDC from clinical 

laboratories were positive for influenza, but influenza activity remained very low compared to the

peak of the season last year. During the same timeframe, detailed data from US public health 

laboratories showed a predominance of influenza B coming out of last season, but over the 

summer there was a dramatic shift to influenza H3N2 viruses with a small number of 

H1N1pdm09 viruses. Overall, these data showed very low activity as well during this time 

period. Reported through the Influenza-Like Illness Surveillance Network (ILINet), 1.2% of 

patient visits were for influenza-like illness (ILI). Compared to other recent seasons, this is 

typical for this time of year.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

42 

Another major change for surveillance this year is that CDC is transitioning away from its 

traditional system for reporting pneumonia and influenza mortality from the 122 Cities system to 

the National Center for Health Statistics (NCHS) mortality surveillance system. These are the 

regular vital statistics data that NCHS collects, which are being made available to NCIRD in real 

time. The data will be presented the same as the 122 Cities data have been reported, showing 

the percent of death certificates that have pneumonia or influenza listed anyplace on the 

certificate and the seasonal baseline and epidemic thresholds, which are modeled using a 

robust regression procedure. One advantage of these data is that when all data are in, NCIRD 

will have virtually 100% of all deaths that occurred in the US within a year of the date of time of 

death. In addition, rather than being reported the week the death certificate is filed, it is possible 

to plot the data by the date of death, which offers a more accurate picture of the timing of 

influenza activity. As of October 15, 2015, through the week ending September 26, 2015, 5.5% 

of the deaths reported to this system had pneumonia or influenza reported someplace on the 

certificate. That is compared to a baseline of 6.2%.

The geographic distribution of influenza as of the week ending October 10, 2015 (Week 40) is 

basically as would be expected at this time of year, with the majority of states reporting either no 

activity or sporadic activity. However, Oklahoma reported local activity, Hawaii reported 

regional activity, and Guam reported widespread activity.

In terms of the Southern Hemisphere vaccine virus selection, the WHO Consultation and 

Information Meeting on the Composition of Influenza Virus Vaccines for the Southern 

Hemisphere 2015 was convened on September 22-24, 2015. During that meeting, it was 

recommended that the following viruses be used for trivalent influenza vaccines in the 2016 

Southern Hemisphere influenza season:

 A/California/7/2009 (H1N1)pdm09-like virus

 A/Hong Kong/4801/2014 (H3N2)-like virus

 B/Brisbane/60/2008-like virus

For quadrivalent vaccines containing two B components, it was recommended that the following 

viruses be used in the 2016 Southern Hemisphere influenza season:

 A/California/7/2009 (H1N1)pdm09-like virus

 A/Hong Kong/4801/2014 (H3N2)-like virus

 B/Brisbane/60/2008-like virus

 A B/Phuket/3073/2013-like virus

The Southern Hemisphere recommendation represents an update in the H3N2 component and 

a switch of influenza B virus lineage for the trivalent vaccine formulation. These updates are not 

the result of significant antigenic drift as was observed last season. Global laboratory data 

continue to indicate that most currently circulating viruses are antigenically similar to the vaccine 

viruses included in the 2015-2016 US vaccines. Considering the H3 viruses in more detail, 

recent H3N2 viruses can be divided into multiple genetic groups as illustrated in the following 

graphic:

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

43 

The A/Switzerland/9715293/13 viruses which is in the Northern Hemisphere vaccine this year 

formulation belongs to the 3C.3a group. A/Hong Kong/4801/14 which was recommended for 

the Southern Hemisphere component belongs to the 3C.2a group. While there are 3C.3a 

viruses still circulating throughout the world, the majority of viruses are in the 3C.2a genetic 

group.

Antigenic characterization of A(H3N2) viruses remains technically difficult. Many of the 3C.2a 

viruses assessed had low or undetectable hemagglutination activity or could not be recovered in 

cell culture at all. This required the use of modified hemagglutination inhibition (HI) and virus 

neutralization assays for analysis. Egg propagation of these viruses can introduce changes in 

the viruses that may affect their antigenicity. 

The following is antigenic cartography data produced from HI assays performed at CDC using 

reference ferret antisera raised to representative viruses from different antigenic groups:

There is a good bit of overlap between the two genetic groups 3C.3a (lime dots), the group to 

which A/Switzerland belongs, and the 3C.2a (red dots), the group to which A/Hong Kong 

belongs. This indicates that there is cross-reactivity between many of the viruses in this groups, 

and that the majority of viruses are antigenically related. However, there are viruses on the 

periphery that are antigenically distinguishable from one another. Comparing this to the older 

3C.2a, 3C.3a, and last season’s A/Texas vaccine viruses represented by the blue dots, there is 

Africa Asia Europe North America Oceania South America

3

15 11

298

177 380

134

48

38

77

40 30

44

14

41

3 8 1 4 1 7 2

1

HA Group 3C.1 3C.2 3C.2a 3C.3 3C.3a 3C.3b

A/H3N2

3C.2a

3C.3a

3C2,3C3

A/Texas/50/2012-cell

A/Switzerland/2013-cell

3C.2a 

representative

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

44 

much less overlap between those viruses and the 3C.2a and 3C.3a viruses, indicating that 

those viruses were more antigenically distinct.

Genetic subgroup 3C.2a viruses are predominating globally. Antigenic characterization using 

reference ferret antisera indicate that 3C.3a and 3C.2a viruses are overall antigenically similar 

but are distinguishable in some cases. A suitable candidate vaccine virus for 3C.2a genetic 

subgroup viruses was not available last February when the Northern Hemisphere vaccine strain 

selection was made, but now there are several 3C.2a candidate vaccine viruses available. 

The influenza B viruses recommended for quadrivalent influenza vaccines did not change. The 

influenza B lineage recommended for trivalent influenza vaccines switched from a B/Yamagata 

lineage to the B/Victoria lineage. B/Victoria and B/Yamagata lineage viruses continue to cocirculate, with B/Yamagata viruses predominating in many countries but the proportion of 

B/Victoria viruses increased in Australia and New Zealand from June 2015. 

In summary, influenza A(H1N1)pdm09, A(H3N2), and both lineages of influenza B viruses 

continue to circulate worldwide. Activity in the US and other Northern Hemisphere countries 

remains low at this time. Recommended viruses for the 2016 Southern Hemisphere vaccine 

differ from the current Northern Hemisphere viruses, but changes represent minor updates and 

are not due to significant antigenic drift. Global laboratory data continue to indicate that most 

currently circulating viruses are antigenically similar to the vaccine viruses included in the 2015-

2016 US vaccines. This suggests that vaccination with Northern Hemisphere influenza vaccine 

should offer protection against the majority of circulating viruses analyzed to date and may offer 

significantly more protection compared to last season’s vaccine. 

Discussion Points

Dr. Belongia requested information about whether there has been any antigenic testing of high 

growth reassortant viruses that are used for vaccine manufacturing and how those compare 

with the WHO reference viruses.

Dr. Jacqueline Katz (NCIRD) responded that the WHO Collaborating Centers routinely compare 

the candidate vaccine viruses with the reference ferret antisera that were produced against the 

parental wild type strains. In order for candidate vaccine viruses to be passed and approved for 

use by a manufacturer, they must be antigenically similar to the recommended strains. That 

has been done and a number of these are posted on the WHO website.

Ms. Stinchfield (NAPNAP) noted that the Influenza WG has discussed whether there is a time 

that is too early to start vaccinating and the duration of protection. She wondered whether 

anything was known about the vaccination status of the individual cases in the South African 

spring B outbreak and H1N1 in Cuba, and whether CDC had any plans to assess late season 

breakthrough disease in people who are vaccinated early in August and September.

Ms. Brammer replied that CDC does not have the vaccination status for the viruses submitted 

from South Africa, or from any of the viruses reported to the WHO system. CDC will be 

conducting vaccine effectiveness (VE) studies to understand VE in the US in the fall, and that 

will be done throughout the season. There will be early season estimates, which would 

represent people vaccinated earlier in the season. Because the plan is to assess the entire 

season, it will be possible to notice any changes that occur late in the season.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

45 

Cost-Effectiveness of High-Dose Versus Standard-Dose

Inactivated Influenza Vaccine in Adults Aged 65 Years and Older

Ayman Chit, MBiotech, PhD (Via Teleconference) 

Sanofi Pasteur

Lesli Dan School of Pharmacy

University of Toronto, Ontario, Canada

On behalf of the authors of the study and Sanofi Pasteur, Dr. Chit thanked ACIP and the CDC 

Influenza WG for the opportunity to present the results of Sanofi Pasteur’s study during this 

session. In addition, he thanked the Office of the CDC Chief Economist for reviewing the study. 

The slides presented during this session were the result of the scientific exchange that they 

have had with the Office of the CDC Chief Economist. The study was published in September 

2015 in The Lancet Infectious Diseases. During this presentation, Drs. Chit and Greenberg 

reviewed the study methods, results, and limitations.

This study was an economic evaluation of High-Dose Fluzone® vaccine, which is an inactivated 

split virus influenza vaccine containing 4 times the antigen content of standard-dose vaccine. 

More specifically, a cost-effectiveness analysis was conducted that compared Fluzone® HighDose vaccine versus standard-dose Fluzone® vaccine. This analysis primarily used data from 

the randomized control study FIM12, an efficacy study that has been presented to ACIP in the 

past that has been published in the New England Journal of Medicine (NEJM) and elsewhere.

At this point, Dr. Chit was breaking up and could not be understood, so Dr. David Greenberg 

delivered the remainder of the presentation.

David P. Greenberg, MD

Vice President, Scientific & Medical Affairs

Chief Medical Officer, Sanofi Pasteur US

Dr. Greenberg apologized for the technical issues, and completed the remainder of Dr. Chit’s 

presentation. He explained that the analysis was primarily from the randomized controlled 

study, which Sanofi Pasteur termed FIM12, which Dr. Chit had mentioned has been presented 

previously to ACIP and to the CDC Influenza WG. The results were published in the NEJM last 

year, and follow-up reports were subsequently published in other journals. Dr. Greenberg 

emphasized that the key feature of the analysis that Dr. Chit performed was from the 

randomized controlled trial of FIM12, so very little modeling or extrapolation of the data was 

required because it was all contained within that efficacy trial. This was a study of nearly 32,000 

seniors who participated in the two-year study. The results are reported from both the 

healthcare payer and societal perspectives, and the latter encompasses the former and adds 

costs associated with workplace productivity. A single influenza season was used as the time 

horizon for assessing healthcare resource utilization and changes in quality of life due to clinical 

events. Lost life years (LY) and lost quality-adjusted life years (QALYs) due to deaths were 

considered up to the life expectancy age. A 3% annual discount rate was used and was applied 

to outcomes that occurred after the first year.

In terms of the basic design of the FIM12 randomized controlled trial (RCT), and how the 

economic evaluation was added on, FIM12 spanned two influenza seasons: 2011-2012 and 

2012-2013. The 2011-2012 season was mild and had a good match between the vaccine and 

circulating strains, while the 2012-2013 season was more severe and had a mismatch between 

the circulating and vaccine H3N2 strains. Participants were enrolled and randomized at the 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

46 

beginning of each season. Study centers collected data on clinical events and health care 

resource utilization from the participants. Data on clinical events experienced by study 

participants were then mapped to corresponding costs and quality of life data. All costs were 

reported in 2014 dollars. To estimate cost-effectiveness, costs and outcomes were compared 

between the two groups. Unlike most cost-effectiveness studies which rely heavily on 

mathematical modeling of the relationship between the vaccine and clinical outcomes, this 

analysis relied on the FIM12 head-to-head RCT to directly inform the impact of these vaccines 

on the clinical outcomes. As noted earlier, little mathematical modeling was needed for this 

analysis.

Two sets of analyses were performed, and subgroup analyses were conducted within each. 

The first set, identified as Scenario 1, involved assessing all of the outcomes collected in the 

study regardless of their relation to influenza. More specifically, this included the cost of

vaccine, medication, hospitalization for any reason, and emergency department (ED) nonroutine urgent care visits following a new respiratory illness. Lost life due to death was 

considered regardless of the cause of death. To emphasize, Scenario 1 involves assessing all 

of the outcomes collected in the study regardless of their relation to influenza. So for example, 

if a study participant was hospitalized due to an accident, that outcome was included in 

Scenario 1 despite its unlikely relationship to influenza. The upside of that strategy is that it 

provides insight into the relative impact of Fluzone® High-Dose in the total cost and the overall 

health of the study population. The downside of this strategy is that it may miss the impact of 

vaccine due to noise generated by the non-influenza related medical events, and there are 

many of those in this population.

To address the downside, a second analysis was conducted and is referred to as Scenario 2. 

Scenario 2 considered only cardio-respiratory clinical outcomes that were considered plausibly 

related to influenza. The feature allowed for the removal of much of the noise generated by 

outcomes not likely related to influenza. For each of these two scenarios, two sub-group 

analyses were performed in subjects who had either one or more pre-specified high-risk 

comorbid conditions, typical high-risk conditions for complications due to influenza, and in 

subjects who were 75 years of age and older.

With regard to the key data collected and used in the economic analysis and evaluation to 

supplement the FIM12 clinical trial, the vaccine prices were provided from the CMS seasonal 

influenza vaccine pricing list: about $12 for Fluzone® vaccine and about $32 for Fluzone® HighDose. The reason the other medications were listed is because the medications were restricted 

to antipyretics and antivirals. Healthcare visit and hospitalization costs were obtained from 

sources that represent Medicare costs. Most notably, it was estimated that the hospitalization 

costs varied from about $1200 per day to just over $9000 per day. That variation was driven by 

the various hospitalization diagnostic codes. Regarding the quality of life data used in the study, 

the investigators began with average utility scores of 0.802 and 0.771 for males and females, 

respectively. These were drawn from the literature. Various medical encounters would then 

reduce the quality of life by varying amounts. For example, the reduction from baseline 

associated with hospitalization equals 0.4272 for the first 3 days and 0.2832 for the remaining 

days until discharge.

Comparing the costs between the two arms of the study presented per participant; that is, the 

total costs for each cost category summed up for each study arm and then divided by the 

number of study participants enrolled in that arm of the study, the price difference between the 

two vaccines was about $20 per participant. In terms of whether there were any cost savings 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

47 

that would offset the $19.75 investment in Fluzone® High-Dose, there was little difference with 

respect to the prescription medications, ED visits, or urgent care visits. However, hospitalization 

costs were $136 per participant lower in the Fluzone® High-Dose group compared to the 

Fluzone® group. This offset the incremental increase in the vaccine cost and resulted in a net 

savings of $116 per participant. This is the most important finding of this study. This considers 

only the cost burden to the healthcare system.

When the scope was widened to include costs from the rest of society, further savings were 

associated with anticipated improvements in the productivity of the Fluzone® High-Dose group 

for a total societal-wide savings of $128 per participant. Regarding the results from the costeffectiveness calculations, Fluzone® High-Dose also generated a higher number of QALYs than 

the standard dose Fluzone® vaccine group. As such, Fluzone® High-Dose dominated Fluzone®

in the cost-effective analysis. In other words, Fluzone® High-Dose was both less costly and 

more effective than Fluzone®. The primary conclusion applies to the other analyses conducted 

as well. Fluzone® High-Dose was both less costly and more effective than Fluzone® in the 

cardio-respiratory outcomes analysis Scenario 2 and in all of the subgroup analyses, which is a 

reminder that the subjects have comorbid conditions and are 75 years of age and over.

A probabilistic sensitivity analysis was performed to help understand the impact of the statistical 

uncertainty of the conclusions, illustrated by the following scatterplots:

Starting with the plot on the left, the horizontal axis represents the difference in the QALYs 

between the Fluzone® High-Dose and Fluzone® groups, so any positive findings (the right side 

of the graph) supports QALY benefits in favor of Fluzone® High-Dose. The vertical axis 

represents the difference in costs between the two vaccines, so any negative readings (the 

lower half of the graph) support cost savings in favor of Fluzone® High-Dose. The red square at 

the center of the dots represents the base case or average. The dots on this graph are the 

points of the statistical distribution of the effectiveness analysis, and that was the bootstrapping 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

48 

with 1000 samples. The red square at the center of the dots represents that average case. The 

one on the left is just to the right of the vertical line and well below the horizontal, and the other 

one is on the right. The left panel represents results from the full analysis set.

Recall that this analysis contains high background noise, as all medical events were included. 

For example, hospitalizations due to injuries or accidents are also in this dataset. The striking 

finding of the dataset is that despite that heterogeneity, 93% of the statistical distribution shows 

that Fluzone® High-Dose provides cost savings, because 93% of the analysis is in the lower half 

of the plot, which represents cost savings in the High-Dose compared to Standard-Dose 

Fluzone®. The right panel represents results from the cardio-respiratory analysis. Here the 

signal to noise was improved, only focusing on the respiratory conditions plausibly related to 

influenza. In other words, the events that were not cardio-respiratory in nature and not likely to 

be related to influenza were stripped out. Now 94% of the statistical distribution falls in the 

bottom right corner region that supports the conclusion that Fluzone® High-Dose is both less 

costly and more effective than Fluzone® vaccine. This was the second most important finding 

from the study.

Hospitalization data were the primary driver of the analysis. Hospitalization event data were all 

collected in the head-to-head RCT, and they were not based on modeling. The costs were 

obtained from Medicare sources, and these represented 95% of the total costs to the healthcare 

payer and 87% of the total societal cost. After hospitalization costs, the vaccine costs and the 

indirect costs were the next two notable cost categories, respectively. However, their 

contribution was minor compared to the cost of hospitalization.

Like any study, this one has standard limitations. First, the evaluation was conducted on the 

FIM12 study population. Therefore, all limitations of an RCT apply. Most notably, the trial did 

not enroll bed-ridden seniors due to practical considerations of the study, and the trial did not 

collect data on indirect protection of vaccine to others in the household or community. Second, 

QALY data were not collected directly in the FIM trial. Instead, QALY data were acquired from 

the literature. Third, some diagnostic codes had to be grouped when estimating the 

hospitalization costs, which was primarily to simplify the exercise of costing the more than 3000 

unique hospitalizations recorded in the FIM12 study. Fourth, disutilities and costs were limited 

to those experienced during the study period. If disutility was experienced by seniors due to a 

hospitalization after the study ended, that was not included.

Discussion Points

Dr. Moore requested clarification that the difference in QALYs, although it was dominated, was 

four ten thousandths. 

Dr. Greenberg replied that all of the analyses were divided across all 32,000 participants. So, a 

reduction of QALY gained there of 0.0004 was averaged across all 32,000 participants.

Dr. Karron asked whether a difference was observed by season and within subgroups, high-risk 

groups, those over 75 years of age.

Dr. Greenberg replied that certainly any time data are cut in a different way, there will be slightly 

different results. He emphasized that they were just modest differences. All of the conclusions 

about Fluzone® High-Dose being less costly and of greater benefit applied in all of the subgroup 

analyses and by season. That conclusion was the same for the very mild 2011-2012 season, 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

49 

as well for the more severe H3N2 season with some mismatch. The conclusions were the 

same by the comorbidity and cardio-respiratory subgroup analyses and by age. While there 

was some variation in the exact dollar amounts, this was not by a magnitude and they were all 

directionally the same.

Dr. Sun (FDA) asked whether any subgroup analyses were performed based on gender in 

terms of this cost-benefit analysis.

Dr. Greenberg replied that such analyses were not performed prospectively as far as he was 

aware, but this certainly could be done.

Dr. Weber (SHEA) asked whether there were any plans to perform this analysis of high-dose 

versus quadrivalent standard-dose. 

Dr. Greenberg responded that an analysis was performed which was more of a modeling study 

based on the literature and what is known about Fluzone® High-Dose and quadrivalent 

vaccines. That analysis is published. In the senior population where influenza B occurs but 

H3N2 is clearly the more severe pathogen and results in more hospitalization, complications, 

and deaths, the analysis clearly showed that in terms of a cost per QALY, Fluzone® High-Dose 

was more cost-effective than quadrivalent vaccine.

Dr. Neuzil (IDSA) asked whether there will be a quadrivalent high-dose in the future and if so, 

whether the price differential between the high-dose and the standard-dose for quadrivalent 

would be similar.

Dr. Greenberg responded that the clinical development program for quadrivalent high-dose 

Fluzone® High-Dose is underway. Sanofi Pasteur is conducting a Phase II study this year, and 

that process is ongoing. Having a high-dose vaccine for the senior population was paramount, 

so that is where Sanofi Pasteur focused its efforts. The quadrivalent vaccines do not provide as 

much benefit in this population, but the process is underway for the high-dose quadrivalent 

vaccine. While he could not comment on price at the moment, he said he would provide it.

Dr. Messonier (CDC SME) asked whether Dr. Greenberg had data showing a sensitivity 

analysis of price to reflect at what point the comparative advantage would fall off.

Dr. Greenberg responded that while he did not have this information with him, his understanding 

of the data and Dr. Chit’s analyses was that it would have to be a very expensive vaccine for the 

cost benefits to disappear or drift down to zero.

Dr. Duchin (NACCHO) recalled that in each of the categories in the QALY analyses, high-dose 

was preferred because it dominated in the analysis. But he also noticed that the difference was 

about four ten thousandths of a QALY between the two vaccines. He asked Dr. Greenberg to 

help him understand what four ten thousandths of a QALY meant.

Dr. Greenberg explained that if a person is hospitalized, there is a reduction of about a 0.4 

QALY in the person’s quality of life during early days of the hospitalization, somewhat less of a 

drop-off in their quality during the latter part of the hospitalization, and probably a little reduction 

occurs after that person goes home. But that is one hospitalization—one dramatic effect on that 

one person’s quality of life. There were plenty of hospitalizations in the study, many of which 

were not related to influenza. When all of the hospitalizations and other medical events that 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

50 

occurred in the high-dose group versus the standard-dose group are combined and averaged 

them among 32,000 people, the difference is small. The difference would be large when 

assessing only the cardio-respiratory events, but if a vaccine provided health benefits so that 

the quality of life was better, even marginally, but cost a lot, the discussion would be about how 

many dollars per QALY that benefit would cost the health system and society. This vaccine 

resulted in less cost. While the difference in the QALYs across 32,000 people who had all sorts 

of medical events occurring during the two years of the study was small, it actually cost the 

medical system less money to provide that vaccine than a standard-dose Fluzone®. 

Dr. Duchin asked why the benefit was found only in hospitalization if it was so dominated by 

cardio-respiratory conditions in general.

Dr. Greenberg responded that this was somewhat due to the design. In this case, it was 

possible to identify all of the cardio-respiratory events that occurred in the trial. When including 

every office visit, ED visit, and non-urgent visit that occurred during the study, it just got diluted 

by all of the noise of everything that was not related to influenza or was not serious. So, that 

was why the cost savings were observed primarily for the serious events.

Adjuvanted Trivalent Influenza Vaccine 

Kelly Lindert, MD

Head, Development

NVS Influenza Vaccines

Dr. Lindert provided an overview of NVS Influenza Vaccines’ adjuvanted trivalent inactivated 

influenza viral vaccine (aTIV). She provided a brief overview of the development of aTIV, the 

mechanism of action of NVS Influenza Vaccines’ adjuvant known as MF59, data on the 

immunogenicity and safety of aTIV in clinical trials, safety data from post-marketing experience, 

data from two observational trials evaluating the effectiveness, and additional data relating to 

the recent A(H3N2) mismatch.

The development program supporting aTIV spans more than 20 years, with the first clinical trials 

initiated in 1992. Since then, aTIV has been reviewed and approved by several health 

authorities. It was first approved for us in Europe in individuals 65 years of age and older in 

1997. In 2011, aTIV was approved in Canada for use in older individuals. In 2015, it was 

approved in Canada for use in children. aTIV is currently approved in more than 30 countries 

worldwide, and to date, more than 76 million doses have been distributed across these 

countries for use in the prevention of influenza. In 2014, Novartis filed a Biologics License 

Application (BLA) seeking US licensure for the use of aTIV in individuals 65 years of age and 

older. These data were reviewed at Vaccines and Related Biological Products Advisory 

Committee (VRBPAC) in September, with a favorable vote by the members of that committee.

Regarding the rationale for development of an adjuvanted influenza vaccine, influenzaassociated deaths remain high in those individuals 65 years of age and older despite 

recommendations for use and the use of influenza vaccines in this age group. This is in part 

due to immunosenescence, or the aging of the immune system. Immunosenescence is a 

deregulation of immune function, which not only increases the incidence and severity of 

infections, but also reduces a person’s ability to respond to vaccination. These two issues 

create a particular unmet need in the older population that adjuvant use can help to address.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

51 

MF59, the adjuvant in aTIV, enhances the immune response to influenza vaccine and has an 

acceptable safety profile. MF59 is a stable oil and water emulsion in which droplets of squalene 

coated in surfactants are suspended in a citrate buffer. Squalene is a naturally occurring 

precursor to cholesterol and is present in the liver, adipose tissue, and skin. The surfactants, 

Tween® 80 and Span® 85, are commonly used for pharmaceutical products and are sourced 

from plants. Overall, it is the droplet structure that is critical for the adjuvant effect of MF59. 

Furthermore, no single component of MF59 individually enhances immunogenicity. Rather, it is 

the combination that is necessary.

The adjuvant’s mechanism of action can be described in three basic steps. First, MF59 

activates dendritic cells and macrophages, attracting monocytes and neutrophils to the site of 

injection. Second, the presence of MF59 leads to differentiation of these cell types. These cells 

transport more antigen from the injection site to the draining lymph node. Third, within the 

lymph node, MF59 leads to T-cell activation and an increased B-cell expansion, with the 

downstream result of increased production of neutralizing, influenza-specific antibodies.

With regard to how this mechanism of action translates into response in the clinical setting, 

MF59 has been evaluated extensively in clinical trials. Data from 58 interventional trials were 

included in the BLA filing. Of these, 39 were performed in individuals 65 years of age and older 

leading to a safety database of over 27,000 individuals. The large number of trials facilitated the 

review of the safety profile of aTIV. However, it is the large pivotal trial, V70_27, that represents 

the primary study evaluating the immunogenicity and safety of aTIV in older adults. Additional 

analyses of immunogenicity were conducted in a grouping of 15 randomized, controlled primary 

vaccination and in 7 revaccination trials. The latter included individuals receiving up to 3 annual 

doses of aTIV or TIV vaccine.

Pivotal study V70_27 was designed to evaluate the immunogenicity and safety of aTIV. This 

study was a randomized, controlled, observer-blinded multi-center trial enrolling 7104 study 

participants 65 years of age and older. The subjects included both healthy individuals and 

those with underlying comorbidities, and the subjects were assigned to 1 of 3 lots of aTIV or to 

non-adjuvanted seasonal TIV. The 3 lots of aTIV were confirmed equivalent and, therefore, 

data from the subjects receiving vaccine from any of these 3 lots were pooled into a single aTIV 

group for comparison with the non-adjuvanted TIV group for subsequent study objectives. Of 

note, the TIV comparator was a US-licensed vaccine with the same antigen content as the aTIV, 

and it is approved for use in older adults. In this trial, individuals received a single dose of 

vaccine on Day 1, representing the start of the treatment phase. The treatment phase lasted 

until Day 22 when the co-primary objectives were evaluated. Participants were followed for 

safety until one year after vaccination. Additional blood samples were taken at Day 181 and 

Day 366 to evaluate antibody responses at later intervals following vaccination. This is referred 

to as persistence.

The primary non-inferiority objective comparing aTIV to the US-licensed comparator was met in 

this pivotal trial. With respect to the comparison of the homologous antibody responses (e.g., 

the antibody responses against antigens included in the composition of the study vaccines), for 

all three homologous influenza strains, the lower bound of the 95% confidence interval for the 

geometric mean titer (GMT) ratio was above 0.67, which is the margin for non-inferiority in this 

study. The lower bound of the 95% confidence interval for differences in vaccine group 

seroconversion was greater than -10%. In this study, an additional objective evaluated antibody 

responses for superiority, defined as exceeding GMT ratios of 1.5 and seroconversion rate 

differences of 10%. Although the study objective was not met, aTIV met these thresholds for 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

52 

the A(H3N2) strains and demonstrated overall a trend of higher antibody responses for the other 

two influenza strains. Antibody responses against unmatched or heterologous influenza strains 

were also evaluated in this trial. Both GMT ratio and seroconversion rates against these two 

heterologous A(H3N2) and one B strain met the non-inferiority criteria. Antibody responses 

were also consistently higher following vaccination with aTIV.

Safety data collected in this pivotal trial included solicited and unsolicited AEs that were 

monitored within the period immediately after vaccination. A subset of the unsolicited AEs were 

monitored for the full year in this older population. These safety assessments demonstrated no 

differences in unsolicited AEs. Of individuals within the aTIV and TIV groups, 1.5% and 1.3% 

died within the year of follow-up, 7% experienced serious adverse events (SAEs) within this 

interval, fewer than 1% of subjects in each vaccine group withdrew from the study due to AEs, 

16% of individuals in both vaccine groups experienced unsolicited AEs within the first three 

weeks after vaccination. Somewhat of a difference between vaccine groups was an increase in 

solicited AEs within a week following vaccination. The most common solicited AEs overall 

included injection site pain, tenderness, myalgia, headache, and fatigue. In these 5 events, the 

events were more commonly reported in the aTIV group as compared to the TIV group. 

Nevertheless, the majority of the events were mild or moderate in severity and of similar 

duration in both vaccine groups.

Additional safety data are available beyond the clinical trial experience. As described earlier, 

aTIV has been licensed outside of the US for over 17 years. Spontaneous reporting of safety 

data are available following the distribution of over 76 million doses of the vaccine. As a general 

note, the ongoing routine surveillance of these spontaneously reported cases has demonstrated 

a safety profile consistent with other licensed influenza vaccines, and without detection of any 

novel safety signals. Furthermore, for the BLA filing, these data were further analyzed for 

reporting of potential adverse events of special interest and adverse events following 

immunization. An analysis comparing reporting in the aTIV database against reporting of these 

cases in the database of another non-adjuvanted influenza vaccine administered to older 

individuals demonstrated no disproportionality for either AEs of special interest or AEs following 

immunization. Of note, no narcolepsy cases have been reported to date with the aTIV vaccine.

Two effectiveness studies have been conducted with aTIV. The first trial is known as the 

Lombardia Influenza Vaccine Effectiveness (LIVE) study, which is a large, multi-season 

community-based observational study in Italy. In this study, older individuals received either

aTIV or a non-adjuvanted influenza vaccine. These individuals were followed prospectively for 

pneumonia- or influenza-related hospitalizations. At baseline, the patients vaccinated with aTIV 

had more comorbidities, showed higher functional impairment, and were 17% more likely to be 

hospitalized prior to study enrollment. However, in spite of this imbalance and after adjusting for 

confounders, the risk of hospitalization for influenza and pneumonia for those receiving aTIV 

was reduced by 25% during the active influenza season.

The second effectiveness study was undertaken in British Columbia, Canada. In British 

Columbia, all influenza tests are analyzed by a central laboratory and positive tests are reported 

to health authorities by law. This lends itself well to a case-control test negative, communitybased study evaluating RT-PCR-confirmed influenza cases. At the conclusion of this influenza 

season, in the community dwelling residents, aTIV was 73% effective versus 42% for TIV, 

leading to a 31% absolute difference between the two vaccines in the prevention of RT-PCRconfirmed influenza. In addition, in older patients with comorbidities in long-term care, aTIV 

effectiveness dropped to 60%, but TIV was reported as ineffective. As a result, the relative 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

53 

benefit of aTIV over TIV was 63% in this population. Also of note, the prevalent influenza strain 

circulating in the year of this study was A(H3N2). 

In earlier discussions with the ACIP WG, NVS Influenza Vaccines was requested to provide 

data on how aTIV performed against last year’s mismatch. Prior to the 2014-2015 Northern 

Hemisphere influenza season, two parallel trials were conducted wherein older individuals were 

vaccinated with either aTIV or a non-adjuvanted seasonal influenza vaccine. The sera from 

these trials were re-evaluated using a microneutralization assay against the vaccine strain, 

A/Texas, and the strain most closely resembling the mismatched A/H3N2/Hong Kong. Higher 

percentages of individuals vaccinated with aTIV demonstrated seroconversion as compared to 

non-adjuvanted influenza vaccine. This was true for both the matched Texas and the 

mismatched Hong Kong strains.

In conclusion, the data gathered to date reflect a positive benefit-risk profile following 

vaccination with aTIV. aTIV was non-inferior to a US-licensed comparator in its pivotal trial. It 

also demonstrated higher homologous and heterologous titers, reduction of influenza-related 

disease in two effectiveness trials, a safety profile similar to both other licensed influenza 

vaccines and other vaccines administered commonly to older individuals, and higher antibody 

titers against a recent relevant mismatched A(H3N2) strain. If approved for use, aTIV will be an 

important additional option for prevention of influenza in adults 65 years of age and older.

Discussion Points

Dr. Belongia noted a couple of trials which assessed repeated vaccination two or three seasons 

in a row. A number of studies have shown evidence that the vaccines received in prior seasons 

may influence one’s response to the current season. He wondered what had been learned 

about the effective prior season vaccination in terms of aTIV.

Dr. Lindert replied that in general, across the 7 revaccination trials conducted, higher antibody 

responses are consistently observed with aTIV. Of note, across those 7 different revaccination 

trials, there were 3 trials where one of the strains remained the same. In other words, they 

wanted to understand the impact if one was repeatedly exposed to the same strain. They

continued to see still higher titers in the aTIV versus TIV recipients. That was the one instance 

where the strain did not change across the 7 revaccination studies.

Dr. Moore asked with repeated annual immunization what was known about any change in the 

AE rate among recipients who have received the vaccine several years in a row.

Dr. Lindert responded that they still note increased reactogenicity with the adjuvanted vaccine 

as compared to the TIV, but the clinical spectrum remains largely the same. The events remain 

mild to moderate, and do not increase in relative frequency relative to TIV. The overall trends in 

terms of the reactogenciity profile remain stable with revaccination, but reactogenicity such as 

pain remains still higher following vaccination with aTIV.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

54 

Dr. Paul Offit (Children’s Hospital of Philadelphia) noted that narcolepsy appeared to be a 

consequence of the squalene adjuvant in the 2009 influenza vaccine, PandemrixTM. A recent 

Science Translational Medicine paper essentially implicated influenza nucleoprotein as having 

molecular mimicry between that and the hypocretin receptor 2. He wondered whether Dr. 

Lindert knew the quantity of influenza nucleoprotein in this vaccine and whether there is a 

nucleoprotein-specific antibody response to this vaccine.

Dr. Lindert indicated that she would have to follow up with precise estimates; however, by and 

large, the nucleoprotein levels are low to nearly undetectable in NVS’s vaccines. The vaccines 

are subunit vaccines, so by nature they are more purified in terms of removal of nucleoprotein 

relative to, for example, split vaccines. She can come back with more precise estimates.

Dr. Paul Offit (Children’s Hospital of Philadelphia) said he thought that in the Science 

Translational Medicine paper, there was a second squalene adjuvant in influenza vaccine, 

Focetria®, which did not have that response because it had much lesser quantities of 

nucleoprotein. 

Dr. Karron wondered whether, now that MF59-adjuvanted vaccine had been licensed in many 

countries for many years, NVS had had an opportunity to assess effectiveness against drifted 

strains as well as antibody response specifically against the drifted strains. She also noted that 

NVS has the blood samples to be able to evaluate duration of protection of antibody response. 

In addition, she asked whether there were plans for a quadrivalent preparation of this vaccine.

Dr. Lindert indicated that to date, mismatched strains have not been evaluated. However, NVS 

presently has an ongoing efficacy study in children that started enrollment two years ago. With 

last year’s mismatch, they expect to have data that should help to inform everyone about how 

well MF59 works against last year’s mismatch in an efficacy setting. That study is in children 

ages 6 months to less than 6 years of age. For brevity, the data related to duration of antibody 

response were not included in this presentation. In the pivotal trial, antibody responses were 

assessed at Day 181 and Day 365. Particularly at Day 181, across all 3 influenza strains, the 

aTIV titers remained higher than the TIV. This trend remained significant at Day 365 only for 

A(H3N2). NVS does have plans for a quadrivalent preparation of this vaccine. The pediatric 

efficacy trial is being conducted with a quadrivalent formulation. In addition, in this quarter, the 

aQIV will be initiated as well, which is in the elderly.

Given that this vaccine has been used for a long time in the European Union (EU), Dr. Walter 

wondered whether there were any longer term surveillance data on repeated dosing.

Dr. Lindert replied that beyond the 7 revaccination trials she mentioned, they do not. The rest of 

the data rest in the post-marketing surveillance data in terms of understanding if there are any 

unusual patterns in the safety of revaccination, for example, of NVS’s adjuvanted versus nonadjuvanted vaccines. Again, no meaningful trends have been observed with use of both 

vaccines over several years.

Ms. Pellegrini asked whether the BLA that is currently pending with FDA was for licensing only 

in the elderly at this point and, if so, whether NVS anticipated filing a BLA at some point in the 

future for children.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

55 

Dr. Lindert replied that the pending BLA is only for the elderly, but they do intend to file the 

quadrivalent vaccine for use in children after the completion of the efficacy study just mentioned. 

This was in discussion and agreement with FDA.

Because the vaccine has been used for so long in other parts of the world, Ms. Pellegrini asked 

whether Dr. Lindert could share any of the factors that went into the company’s decision to 

delay seeking approval in the US for so long.

Dr. Lindert explained that this vaccine has been in the hands of a few different vaccine 

manufacturers through the years. When Novartis originally acquired the MF59-adjuvanted 

vaccine, they were very enthusiastic about seeking US licensure and started the conversations 

with the FDA. Prior to that, there were different strategic prerogatives for the predecessors.

Related to Dr. Karron’s question, Dr. Duchin (NACCHO) asked whether there are any data on 

the relative effectiveness of adjuvanted versus non-adjuvanted looking at the time since 

vaccination over the course of one season.

Dr. Lindert responded that they do not have those data at this point. There will be further 

exploration in the efficacy trials to understand that. Because the immunogenicity data show 

some interesting trends, they would like to determine whether that translates into additional 

benefit.

Dr. Schaffner (NFID) asked whether it was correct that the comparator vaccine has been TIV in 

all of the clinical trials and that aTIV has not been compared with high-dose vaccine.

Dr. Lindert confirmed that this was correct.

Dr. Jeanne M. Santoli

Immunization Services Division

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention

During this session, Dr. Santoli presented an update on the 2015-2016 US influenza vaccine 

supply. Manufacturers have estimated that as many as 171 to 179 million doses of influenza 

vaccine will be available this season, depending upon yield, lot release, and demand for 

product. To put that into perspective, 147.8 million doses were distributed last season. The 

highest number of doses distributed in a single season was 155.1 million doses, which was 

during the 2010-2011 season.

Distribution began in August 2015 and is anticipated to continue throughout December 2015. 

As of October 9, 109.4 million doses have been distributed, which is similar to this time last 

year. The following graphic depicts the cumulative doses of influenza vaccines distributed by 

month, by season for the 2004-2015 compared to the 2015-2016 season:

Vaccine Supply

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

56 

Some distribution delays are occurring for specific vaccines from MedImmune and Sanofi 

Pasteur. For MedImmune, all doses originally pre-booked will be produced to fill orders. 

Distribution of FluMist® Quadrivalent began in September and will continue throughout 

December. Partial shipments are being used to distribute vaccine. For Sanofi Pasteur, all 

doses originally pre-booked will be filled. Distribution of Fluzone® in unit dose vials, multi-dose 

vials, and Intradermal Fluzone® is complete. Multi-dose vials and intradermal vaccine supply 

remain available for immediate shipment. Distribution of pre-booked Fluzone® in prefilled 

syringes, including the pediatric 0.25mL syringes, is ongoing and will complete by the end of 

November. For older adults, Fluzone High-Dose® Vaccine will be complete in early November. 

Partial shipments are being used to distribute vaccine.

CDC’s Vaccine Supply/Shortage Webpage can be found at:

http://www.cdc.gov/vaccines/vac-gen/shortages/default.htm

Discussion Points

Dr. Karron requested that the manufacturers comment more specifically on the reasons for the 

delays, problems, and solutions where possible.

Dr. Phil Hosbach (Sanofi Pasteur) indicated that there are now many different “flavors” of 

Fluzone® vaccine, so the process for filling and packaging is much more extensive and 

complex. However, Sanofi Pasteur is only two to three weeks behind original projections with 

most of its vaccines. The good news is that Fluzone High-Dose® Vaccine orders have 

increased. The confidence in patients and providers has exceeded Sanofi Pasteur’s 

expectations. This year it is anticipated that 50% of all seniors 65 years of age and older who 

receive an influenza vaccine will receive the high-dose vaccine. That is going very well. More 

than 50% of the pediatric syringes have been shipped. Of the estimated 65 million doses of 

vaccine Sanofi Pasteur anticipated shipping this season, 50 million have already been shipped. 

The remainder will be shipped by the end of November.

Dr. Allyn Bandell (MedIummune AstraZeneca Medical Affairs) reported that they had some 

unforeseen challenges in production of FluMist® this year. To date, 5 million doses have been 

shipped and 4 to 5 million doses are anticipated to be shipped by the end of November. 

Production of FluMist® will continue through the season to meet any late season needs, which is 

supported by CDC. Earlier this year, they had longer to develop the H1N1 strain that was 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

57 

included in this year’s vaccine. Recently, a number of lots had H3N2 potency that was outside 

of specifications. It is important to note that nothing that has entered or will enter the market 

has exceeded specifications. All products have passed internal quality assurance measures.

Dr. Sawyer (PIDS) pointed out that for the pediatric 0.25mL dose for young infants, there is a 

single manufacturer. California has a law that prohibits the use of thimerosal -containing 

vaccines, so they must wait for that vaccine to immunize infants. Since most infants need two 

doses of vaccine, he expressed his hope that the company would reprioritize the order of their 

doses and distribute the young pediatric dose first. Otherwise, an even better solution would be 

for another manufacturer to produce this vaccine as well for this age group so there would be 

some competition.

Dr. Phil Hosbach (Sanofi Pasteur) indicated that Sanofi Pasteur tries to balance its production 

amongst all of the varieties of influenza Fluzone®. The trivalent vaccine will no longer be 

produced, which will certainly be helpful. They cannot prioritize based upon laws of states, but 

do prioritize based upon the orders received. Fortunately, over 50% of the vaccine has been 

distributed across the country in a variety of healthcare settings. That should have gotten at 

least one dose for every child. Two doses are needed of the 0.25mL dose. Hopefully, there

was enough for everyone to get started. He promised that the remainder of orders would be 

fulfilled before the end of November.

Dr. Leonard Friedland (GSK) reassured Dr. Sawyer that GSK is working on an influenza vaccine 

licensed down to 6 months of age. Information has been shared with the Influenza WG. GSK 

plans to proceed ahead, so hopefully there will soon be two manufacturers.

Dr. Duchin (NACCHO) asked whether there are any current vaccine effectiveness studies of 

high-dose vaccine.

Dr. David Greenberg (Sanofi Pasteur) replied that there is an ongoing trial by an independent 

investigator with funding from Sanofi Pasteur who specifically studied high-dose vaccine in 

nursing homes. That study was conducted over two seasons, and the preliminary results were 

recently presented in San Diego. His publications are pending the receipt of Medicare data, 

which is a struggle. As soon as he receives those data, he will be able to complete his analyses 

and publish the results. During the first season of the study, which was an H3N2 year, there 

was a 30% reduction in all-cause hospitalizations from nursing homes. During the second 

season, which was an H1N1 year, there was a 7% reduction in all-cause hospitalizations. 

There was also a recent presentation during a conference in San Francisco on another totally 

independent cost-effectiveness analysis of Fluzone High-Dose® Vaccine versus standard dose 

vaccines from the University of Pittsburg. An additional study, the CDC/FDA/CMS of vaccine 

effectiveness for outpatient and inpatient care for influenza that is published, showed a 22% 

reduction in outpatient and inpatient influenza cases among over 900,000 high-dose recipients 

compared to 1.6 million standard dose recipients.

Dr. Kelly Moore commented that the unfortunate complication of the MedImmune challenges 

this year has been particularly difficult for programs conducting school-located vaccination 

clinics. There are numerous challenges from the outset with scheduling with schools, which in 

themselves must be overcome. FluMist® is a popular product in those settings understandably 

with children who are unaccompanied. Unfortunately, the delay has resulted in varying degrees 

of cancellations or reductions in immunizations given in those settings. She suggested 

assessing the impact of delays operationally in terms of coverage rates among those age 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

58 

groups later in the season to determine whether there is an actual impact in coverage rates due 

to changes in supply availability in the early part of the season.

Dr. David Weber (SHEA) indicated that the same problem occurred with immunization of their 

healthcare workers. When schedules are set up in August and then there are shortages, it is a 

major problem because they require all of their healthcare personnel to be immunized by 

December 1st. Late deliveries into November and December are well beyond the time for them 

to meet their requirements for immunization.

Introduction

Allison Kempe, MD, MPH

Chair, ACIP HPV Vaccines WG 

Dr. Kempe said that she was very honored to be asked to Chair the HPV Vaccines WG. Dr. 

Kempe described some of the history of the work of the HPV Vaccines WG over the past one to 

two years regarding 9vHPV vaccine. ACIP reviewed data on the 9vHPV vaccine during 2014. 

The vaccine was then licensed at the end of that year. 9vHPV vaccine was recommended by 

ACIP during the February 2015 meeting. An MMWR Policy Note was published in March 2015.

The February 2015 ACIP meeting was abbreviated due to inclement weather and one issue, 

9vHPV for persons who completed an HPV vaccination series with 2vHPV or 4vHPV, was not 

discussed. In June 2015, the WG reviewed additional 9vHPV vaccination information for those 

previously vaccinated, including the burden of disease, immunogenicity data from the trial of 

9vHPV among persons who previously completed a 4vHPV series, and cost-effectiveness. 

Questions/answers were drafted to be posted on the CDC website regarding this issue were 

discussed. During that meeting, there was discussion of reviewing this issue again using 

GRADE and the WG was asked to re-discuss this subject. After the meeting, the 

questions/answers giving guidance to vaccine providers were posted and there was an 

announcement in the MMWR in July 2015 alerting readers about the posting.

The document “Supplemental Information and Guidance for Vaccination Providers Regarding 

Use of 9-Valent HPV Vaccine,” links from the ACIP website, and the announcement in the 

MMWR state that there is no ACIP recommendation for routine additional 9vHPV vaccination of 

persons who previously completed a quadrivalent or bivalent vaccination series. Information is 

provided about the safety and immunogenicity of additional vaccination.

After the June 2015 meeting, the HPV Vaccine WG re-discussed 9vHPV vaccine for persons 

who completed an HPV vaccination series. There were discussions with other professional 

groups including AAP, Society for Adolescent Health and Medicine (SAHM), and the AAP 

Committee on Infectious Diseases (COID). The WG also reviewed additional transition issues. 

Almost all members felt that this issue should not be brought back to ACIP during the October 

2015 meeting.

Human Papillomavirus (HPV) Vaccines

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

59 

During this session, presentations were given on the following topics:

 HPV vaccination coverage in the US, National Immunization Survey (NIS)-Teen 2014

 Programmatic strategies to increase HPV vaccine coverage

 HPV vaccine safety

 Monitoring the impact of the HPV vaccination program and future WG plans

HPV Vaccine Coverage in the US, National Immunization Survey-Teen (NIS-Teen) 2014

Sarah Reagan-Steiner, MD, MPH

Medical Officer, Assessment Branch

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention

Dr. Reagan-Steiner’s presentation included an overview of the NIS-Teen, discussion of the 

revised definition of adequate provider data implemented in 2014, and an update on HPV 

vaccination coverage among adolescents in the US.

The NIS-Teen is an annual survey implemented in 2006. It is a random digit dial (RDD) 

telephone survey of landline and cell phone numbers. Parents of adolescents 13 through 17 

years of age are interviewed to obtain sociodemographic information about the adolescent and 

the household. All estimates are based on provider reported vaccination histories from 

adolescents with adequate provider data (APD). The APD definition was revised for the survey 

conducted in 2014. This changed the criteria for inclusion in the analytic sample. The revised 

APD definition was applied retrospectively to the 2013 NIS-Teen data to assess its impact on 

coverage estimates and to inform the approach to the 2014 analyses.

Regarding why this assessment was important, prior to 2014, determining whether an 

adolescent had APD was based on a comparison of household and provider reported 

vaccination history. In 2014, most vaccination history questions were removed from the 

household questions in an effort to shorten the questionnaire and improve survey response 

rates, so this comparison was no longer possible. To have APD prior to 2014, if an adolescent 

was not completely unvaccinated by household report, they had to meet a variety of criteria. In 

summary, if the adolescent was not up to date and there was disagreement between the 

household and provider reported history, they were excluded. For the definition implemented in 

2014, which is the same definition that is currently used by the NIS, adolescents are included in 

the sample if they are either completely unvaccinated by household report or have one or more 

vaccine doses by provider report.

Revised 2013 estimates were calculated after applying the revised APD definition. These were 

lower than the original published estimates. Percentage point differences ranged from 0.6 for 

one or more doses of HPV vaccine in females, to 2.2 for two or more doses of MMR. Given 

these differences, it was determined that 2014 NIS-Teen estimates, which would use the 

revised APD definition, would not be comparable to those previously published. As a result, 

changes in coverage between the 2013 and 2014 NIS-Teen are best measured by comparing 

estimates that used the same revised APD definition. This was the approach used for the data 

presented during this session [http://www.cdc.gov/vaccines/imz-managers/coverage/nis/ 

teen/apd-report.htm].

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

60 

In the 2014 NIS-Teen, the national sample included 20,827 adolescents from the 50 states and 

the District of Columbia (DC). Of these, 54% were from the landline and 46% were from the cell 

phone sampling frames. Response rates were 60.3% for landline and 31.2% for cell phone 

frames, and 57.1% of adolescents from landline and 52.3% from cell phone sample had APD. 

In terms of the trends in vaccination coverage from 2006 through 2014, there were two 

estimates for 2013, the originally published and the revised estimates. In 2014, there were 

increases in coverage for all vaccines routinely recommended during adolescence versus the 

2013 revised estimates. However, a notable gap remained between coverage with Tdap and 

MenACWY vaccination and HPV vaccination in females and males. In 2014, among females, 

coverage with one or more HPV vaccine doses was 60.0% and for three or more doses was 

39.7%. These were increases of about 3 percentage points for each HPV vaccine dose from 

the 2013 revised estimates. This was the second consecutive year of increases in HPV 

vaccination coverage in females. Among males, coverage with one or more doses was 41.7%, 

and with 3 or more doses was 21.6%. These were larger increases at around 8 percentage 

points compared to 2013 [MMWR 64(29);784-792].

In 2014, there were differences in vaccine coverage by poverty status. Coverage with each 

HPV vaccine dose was higher among adolescents living below the poverty level compared with 

those living at or above the poverty level. The finding of higher coverage with three or more 

doses among females below the poverty level had not been observed since 2011. Note that 

coverage being higher among adolescents living below poverty is different from the pattern 

observed for many childhood vaccines where coverage is lower for children below the poverty 

level. Differences were also observed in HPV vaccine coverage levels by race/ethnicity. 

Coverage for each dose of HPV vaccine was higher among Hispanic as compared to white nonHispanic adolescents. Coverage with one or more doses of in both females and males, and 

with two or more doses among females was higher in black non-Hispanic adolescents 

compared with their white non-Hispanic counterparts [MMWR 64(29);784-792].

The following map shows the considerable variation in coverage with one or more doses of HPV 

vaccine among females by state. States with higher coverage are in darker blue, while those 

with lower coverage are in white. Coverage ranged from 38% Kansas to 76% Rhode Island; 

while not shown here, Philadelphia had the highest local area coverage at 80%, and in Puerto 

Rico coverage was 76% [MMWR 64(29);784-792]:

 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

61 

Similarly, the following map shows that coverage with one or more doses of HPV vaccine 

among males also varied by state. Coverage ranged from 23% in IN to 69% in RI [MMWR

64(29);784-792]:

 

While nationally modest but significant improvement was observed in HPV vaccination coverage 

in females, seven jurisdictions (DC, Georgia, Illinois, Illinois-Chicago, Montana, North Carolina, 

Utah) achieved larger significant percentage point increases in coverage, 6 for 1 or more and 6 

for 3 or more HPV vaccine doses. This included 5 jurisdictions (DC, Georgia, Illinois, Chicago, 

Utah) that benefited from 2013 federal funding to increase HPV vaccination coverage among 

adolescents. Project periods for this funding began in late September 2013. Activities were 

subsequently conducted in a timeframe that could have impacted 2014 coverage [MMWR

64(29);784-792].

HP2020 objectives include targets for coverage with three or more HPV vaccine doses among 

adolescents 13 through 15 years of age. In terms of trends in coverage with three or more 

doses in this age group by survey year, very gradual progress is observed over time. Compared 

with 2013 revised estimates, no improvement was observed among females in 2014. Coverage 

was low and far below the target at 34.4%. While coverage improved among males, it was still 

low at 20.6% [NIS-Teen 2008-2014].

A recommendation for HPV vaccination is important. Improving the provision of strong, ageappropriate recommendations for HPV vaccination by clinicians has been a key part of the 

efforts to improve vaccination coverage. In 2014, the percent of parents reporting receipt of 

provider recommendations increased for both girls and boys. Notably, however, this shows that 

approximately 30% of girls and 50% of boys did not receive a recommendation. This leaves 

room for improvement [Unpublished NIS-Teen 2013 (Revised) and 2014 data].

Parental attitudes toward HPV vaccination are also relevant. Among unvaccinated adolescents 

whose parents had no intention to vaccinate in the next 12 months, the top 5 reasons why 

included: not needed/necessary, safety concerns/side effects, lack of knowledge, not 

recommended, and not sexually active. Though there is no predominant reason, the most 

common reason was that the vaccine is not felt to be needed or necessary. There were some 

differences by gender in other reasons. A higher percentage of parents of girls cited safety 

concerns/side effects. A higher percentage of parents of boys indicated that it was not 

recommended. This may be due in part to there being some males in the sample who were 13 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

62 

years or older when the routine recommendation for males was issued in 2011 [Unpublished 

NIS-Teen 2014 data].

Receipt of HPV vaccine at the recommended age of 11 through 12 years is best measured by 

examining coverage by age 13 years by birth cohort using NIS-Teen data that has been 

combined over multiple survey years. These data were published in 2014 for one or more HPV 

vaccine doses among females only, and include information from the 2007 through 2013 NISTeen survey years. Coverage with one or more doses by age 13 years increased on average 

5.8% with each birth cohort, reaching 47% for females born in 2000 (those who turned 13 in 

2013). This demonstrates the challenges associated with improving HPV vaccine series 

initiation at the recommended age. Part of this challenge has been missed opportunities. A 

missed opportunity is defined as a healthcare encounter where at least 1 vaccine is 

administered but not all indicated vaccines are given. Coverage with 1 or more HPV vaccine 

doses by 13 years of age could have reached 91% for females born in 2000 if these missed 

opportunities were eliminated [MMWR. 2014; 63:620-4].

In summary, national HPV vaccination coverage increased in 2014, but remains lower than 

Tdap and MenACWY, suggesting persistent missed opportunities for HPV vaccination. Of note, 

the impact of recent interventions aimed at improving age-appropriate HPV vaccination at 11 

through 12 years was not yet measurable by the 2014 NIS-Teen, given that the survey 

assesses coverage in adolescents aged 13 through 17 years. Coverage is higher for 

adolescents living below the poverty level and Hispanic and non-Hispanic Black adolescents. 

There was considerable variation in HPV vaccine coverage by state and local area. We 

continue to face challenges in HPV vaccination coverage among younger adolescents. 

However, seven public health jurisdictions achieved improvement in HPV vaccination coverage 

among females and strategies used can inform activities elsewhere.

Programmatic Strategies to Increase HPV Vaccine Coverage among U.S. Adolescents

C. Robinette Curtis, MD, MPH

Medical Officer, Immunization Services Division 

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention

Dr. Curtis emphasized that improving HPV vaccination coverage among adolescents is an 

agency and division priority. During this session, she provided brief background information, 

reviewed what worked for the jurisdictions with increases in HPV vaccination coverage among 

females, shared some related highlights of a selected initiative, and discussed the challenges 

and opportunities moving forward.

Immunization Services Division (ISD) strategies to increase HPV vaccination coverage include 

supporting state and local immunization programs, mobilizing partners and stakeholders, 

strengthening provider commitment, improving and utilizing systems, and increasing public 

awareness. Consistent with these division strategies, CDC has provided technical assistance 

and Prevention and Public Health Funds (PPHF) to 22 awardees. On the following map, the 11 

awardees that received funding in late 2013 are shown in gold and those funded in August 2014 

are in green:

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

63 

Of the seven public health jurisdictions that Dr. Reagan-Steiner mentioned with improvements in 

HPV vaccination coverage, five were PPHF HPV immunization awardees. The four 2013 

awardees (DC, Chicago, Georgia, and Utah) with increases were able to conduct their activities 

in 2013 and 2014 in a timeframe and with activity target groups that could have impacted NISTeen estimates. Illinois and Chicago program leaders agree that Chicago activities likely 

account for the coverage increases observed for Illinois, which did not receive its award until 

August of 2014. Although the PPHF HPV Immunization awardees overall are in different stages 

with their implementation and evaluation activities, all have worked to increase HPV vaccination 

coverage through activities in the five areas specified in the Funding Opportunity 

Announcement (FOA). Dr. Curtis reviewed each of the activity areas below and provided a brief 

example for each to illustrate how awardees were implementing their activities. The activity 

areas are:

 Developing a jurisdiction-wide joint initiative with immunization stakeholders 

 Implementing a comprehensive communication campaign targeted to the public

 Implementing Immunization Information System (IIS)-based reminder / recall for adolescents 

aged 11 through 18 years

 Using assessment and feedback to evaluate and improve the performance of immunization 

providers in administering the 3-dose HPV vaccine series consistent with current ACIP 

recommendations

 Implementing strategies targeted to immunization providers to:

 Increase knowledge regarding: HPV-related diseases (including cancers), and HPV 

vaccination safety and effectiveness

 Improve skills needed to deliver strong, effective HPV vaccination recommendations

 Decrease missed opportunities for timely HPV vaccination and series completion 

 Increase administration of HPV vaccine doses consistent with current ACIP 

recommendations

In describing stakeholder engagement, Dr. Curtis showed a slide illustrating that stakeholders 

are varied and have included partners such as local chapters of the American Academy of 

Pediatrics, the American Academy of Family Physicians, the American Cancer Society, 

immunization coalitions, public school systems, insurers, pharmacies, and other organizations. 

In illustrating elements of communications campaigns, Dr. Curtis noted that the campaigns have 

typically included varied components, with the slide highlighting print and outdoor ads, radio and 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

64 

television, public transportation ads, social media (including Twitter and Facebook), and digital 

media, including Pandora. With respect to reminder / recall, Dr. Curtis noted that reminder/recall 

involves informing members of a target population that one or more vaccinations are due 

(reminders) or late (recall).

In describing the AFIX activity area, Dr. Curtis noted assessment and feedback entails 

retrospectively assessing providers’ performances in delivering one or more vaccinations to a 

client population and giving this information (feedback) to providers, so that providers can 

improve their performance and vaccination coverage within their practices. Assessment and 

feedback are two of four key strategies to a quality improvement program known as AFIX. This 

AFIX website (http://www.cdc.gov/vaccines/programs/afix/index.html) allows all immunization 

awardees to access CDC guidelines and materials as they seek to engage providers. In 

describing an example of strategies targeted to immunization providers, Dr. Curtis noted that the 

Minnesota Department of Health developed a series of videos on delivering effective HPV 

vaccination recommendations. These videos are being used by partners for teaching and talks 

across the country. (As of 1/8/16, these videos are currently available at: http://www.health. 

state.mn.us/divs/idepc/immunize/hcp/adol/hpvvideos.html) 

Regarding what worked for the seven public health jurisdictions with improvements in HPV 

vaccination coverage, Dr. Curtis noted that some of what she would describe during her 

presentation was included in the July 2015 MMWR NIS-Teen article referenced in presentation 

slides (MMWR 64(29);784–792). Varied combinations of interventions were identified as 

important by six of the seven jurisdictions. Most of the identified activities are as follows:

Activities Specified in PPHF FOA

 Joint initiatives with cancer prevention and immunization stakeholders

 Public communication campaigns

 IIS-based reminder / recall

 Assessment and feedback 

 Conducting activities consistent with federal AFIX guidance

 Ensuring clinical practice decision makers participate

 Including a clinician-to-clinician educational component 

 Provider and practice-focused strategies aimed at improving HPV vaccination administration 

consistent with ACIP recommendations

Other Activities

 Using all opportunities to educate parents and clinicians about the importance of routine 

HPV vaccination at ages 11 through 12 years

 Incorporating HPV vaccination into cancer control plans

Note that the first five activities listed here are activities specified in the PPHF FOA. While it 

was anticipated that these would be useful, it was helpful to confirm with the jurisdictions that 

the activities worked and resulted in increases. With the exception of large communication 

campaigns, these are all activities that can be undertaken as part of routine programmatic work. 

Dr. Curtis highlighted that “Assessment and Feedback” emerged as having been integral to the 

successful efforts in North Carolina and three of the 2013 HPV immunization awardees (with the 

characteristics of the most effective AFIX including conducting activities consistent with federal 

AFIX guidance, ensuring clinical practice decision makers participate, and including a clinicianto-clinician educational component). Provider and practice-focused strategies were identified as 

important by six jurisdictions, and these same jurisdictions also stressed the utility of using all 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

65 

opportunities to educate parents and clinicians about the importance of routine HPV vaccination 

at age 11 through 12 years. An example of using all opportunities includes emphasizing HPV 

vaccination in communications about school vaccination requirements. Incorporating HPV 

vaccination into cancer control plans also appears to be a best practice that can bring together 

stakeholders and create an imperative for increasing HPV vaccination coverage.

A more recent initiative includes multiple partnership cooperative agreements focused on 

increasing HPV vaccination. These cooperative agreements were initially funded in late 2014 

with the following national partners:

 American Academy of Pediatrics (AAP) 

 American Cancer Society (ACS)

 Academic Pediatric Association (APA) 

 National Area Health Education Center Organization (NAO)

 National Association of County and City Health Officials (NACCHO)

This map shows where funded partners are planning to target their activities, as well as 

locations of PPHF HPV Immunization awardees. In states with overlap, work is being done to 

ensure collaboration among funded partners and awardees:

Image Courtesy of the American Cancer Society 

In the context of the data and initiatives shared during this session, there are a number of 

opportunities and challenges moving forward. Evolving recommendations and related issues 

can make programmatic planning and execution difficult and might decrease interventions’ 

impacts. For example, the transitions related to 9vHPV use likely affected vaccination delivery 

this year. Evaluating the impacts of interventions can be difficult, given that increases in 

immunization coverage are hard to achieve in short time horizons; other process and outcome 

measures may be difficult to interpret; and the impact of interventions promoting adherence to 

routine recommendations at age 11 through 12 years are not measurable by the 2014 NISTeen. The fact that five of the PPHF HPV immunization awardees had measurable 

improvements in vaccination coverage as an outcome measure so quickly was exciting, but 

unexpected, by evaluation experts. Some PPHF HPV immunization awardees are still in the 

process of both implementing and beginning to evaluate their activities, so the data that we 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

66 

have available are early. Both implementation and evaluation are affected by competing 

demands. The establishment of partnership cooperative agreements has created more 

opportunities for collaboration in many arenas, including state and local jurisdictions.

From the early data and lessons learned so far, it is helpful from a strategic perspective to begin 

to define generalizable, promising practices that can be integrated into routine programmatic 

activities. These include leveraging opportunities for partnership engagement and collaboration; 

conducting Assessment, Feedback, Incentives, and eXchange (AFIX) consistent with CDC 

guidance and, when feasible, enhanced by clinician-to-clinician education; incorporating HPV 

vaccination into cancer control plans; and using all opportunities to educate parents and 

clinicians about the importance of routine HPV vaccination at ages 11 through 12 years. Based 

on the experiences of six of the seven jurisdictions with improvements in HPV vaccination 

coverage among females in 2014, these interventions appear to be most effective in 

combination, but recent experiences suggest that any one of them would be a useful place to 

start for any jurisdictions and stakeholders who would like to join in increasing HPV vaccination 

coverage among our nation’s adolescents.

Discussion Points

Dr. Bennett asked whether any lessons could be learned from the fact that reverse disparities 

are observed with respect to HPV vaccination rates in different groups, and whether 

consideration has been given to why that might be the case. She also requested elaboration on 

integration with cancer control activities.

Dr. Reagan-Steiner responded that the reverse disparity patterns are important to explore. It is 

likely that multiple factors contribute to the patterns observed, potentially due to differential 

Vaccines for Children (VFC) eligibility in children below poverty and in particular racial and 

ethnic groups. This echoes back to an analysis of 2011-NIS Teen data, on which Dr. Curtis was 

the lead author, in which teens who were VFC-eligible and on Medicaid had higher 1- and 3-

dose HPV vaccination coverage than privately insured teens. There are also likely differential 

patterns of parental acceptance and provider practices by poverty and by race/ethnicity, which 

definitely merit further exploration.

Regarding integration with cancer control programs, Dr. Curtis said it seemed like it would be 

intuitively obvious that these entities would work together. However, sometimes they are not 

historically working together because this might be their first opportunity beyond some hepatitis 

B work in which the topic of vaccination reaches into the cancer prevention realm. Sometimes it 

is as simple as just getting the discussions started between the different entities within the same 

health department, which can then lead to identification of synergies. The national partnership 

cooperative agreements are also very fortunate, and other organizations are interested in 

working together. The PPHF awards created impetus for bringing these organizations together, 

having stakeholder meetings, and identifying activities to work on together. Working on cancer 

control plans, for example, can bring partners together. However, it is important that cancer 

control plans are developed consistent with ACIP guidelines. That is sometimes a missing 

piece.

Dr. Bennett pointed out that in most places, there are breast and cervical cancer control 

programs. Yet, those programs have not thus far integrated HPV vaccination into their 

activities. She wondered whether consideration has been given to this.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

67 

Dr. Curtis replied that, for at least some of the PPHF HPV immunization awardees, there have 

been partnerships with local National Breast and Cervical Cancer Early Detection Programs 

[which are funded through CDC’s Division of Cancer Prevention and Control (DCPC)]. For 

example, one of the National Breast and Cervical Cancer Early Detection Programs is paying 

for the printing of materials for dissemination by a PPHF HPV Immunization awardee. Most of 

the emphasis of HPV vaccination at this point is for those 11 through 18 years of age and the 

overlap in ages, given that the National Breast and Cervical Cancer Early Detection Program 

serves 18 years and older, is somewhat limited.

Dr. Belongia indicated that the Marshfield Clinic Health System (MCHS) receives some 

supplemental funding to allow them to work to improve HPV vaccination coverage within the 

MCHS system, at the same time the State of Wisconsin is engaged in its own initiative. MCHS 

engaged its quality improvement group. There is a Healthcare Effectiveness Data and 

Information Set (HEDIS) measure for this, given that it is considered important from a quality 

improvement perspective. They discovered that this was being considered to some extent, but 

limited efforts were being made. By working with the quality improvement group, MCHS was 

able to change much of what they were doing in terms of their recommendations to the clinics 

and reminder / recall, which they believe will lead to an increase coverage. Quality 

improvement is probably an area in which there can be synergy.

Dr. Curtis noted that the Georgia Department of Public Health (GDPH), as part of their PPHF 

HPV Immunization award activities, had worked with a major health system in the Georgia area 

to implement some quality improvement strategies as well. That seemed to be very helpful and 

has been featured on an AAP webinar by the Georgia chapter. If it is feasible from the MCHS’s 

perspective to disseminate that information, that would be very powerful. There is a pending 

effort in North Dakota to do something similar. Having the benefit of lessons learned from other 

organizations would be tremendously valuable.

Dr. Reingold pointed out that countries as diverse as Brazil, Rwanda, and the UK conduct 

school-based HPV vaccination. There are a number of school-based influenza immunization 

programs in the US. He was curious to know which, if any, of the states have tried schoolbased HPV vaccination, and what their experience has been. If none of them have, he 

wondered why.

Dr. Curtis replied that the Rhode Island Department of Health is embarking on an expansion of 

their Vaccinate Before You Graduate (VBYG) program in middle schools. It is interesting that 

when they tried to share that plan with the area providers and invited them to refer their patients 

to these pending programs in middle schools, there was some push-back. That points to one 

challenge. Another challenge is with the administration of a series. With an influenza program, 

all-comers are presumable not vaccinated during a given season, which makes it somewhat 

less challenging than trying to figure out where children might be in terms of their completion of 

the HPV vaccination series.

Dr. Kempe indicated that Colorado conducted a fairly successful school-based vaccination

program. The most difficult part was billing because this is an expensive vaccine that requires a 

full billing program, unlike with influenza vaccine programs in which vaccine has been donated. 

In her research, the two most rapid ways to increase rates have been centralized reminder / 

recall using an IIS and standing orders. She wondered whether any of these programs used 

those methods.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

68 

Dr. Curtis responded that centralized IIS-based reminder / recall was encouraged for the FOA. 

There are some jurisdictions in which there are political constraints in terms of conducting 

centralized reminder / recall. In those contexts, some jurisdictions have opted to pursue the 

provider-based approach. Some jurisdictions feel strongly that they want to build capacity for 

providers to perform their own reminder / recall, and have that become integrated into routine 

practice. One reason she did not mention IIS-based reminder / recall in general in her 

conclusions was because that has probably been the hardest of the five areas for grantees to 

implement, in part due to infrastructure challenges with their IIS systems. This is very much in 

the implementation and evaluation phase. Some jurisdictions already seem to have very 

promising data in terms of the effectiveness of their centralized reminder / recall, which is very 

exciting.

Dr. Moore offered the encouraging thought that perhaps the VFC program and the streamlining 

of access is a reason for the reverse disparity with the poverty level. It is a credit to the VFC 

program that it streamlines and simplifies access to vaccines immediately upon introduction to 

the VFC formulary. School-located clinics are easier done all or nothing. Trying to have some 

school-based and some private sector-based administration with this series is very challenging, 

particularly with regard to the cost of the vaccine and the complexity of VFC versus private 

insurance in the school setting. In her experience, the collaboration with cancer programs in 

Tennessee, where she Co-Chairs Cervical Cancer Free Tennessee activities along with the 

breast and cervical cancer program at the state level, awareness is raised jointly of the current 

screening guidelines for cervical within OBGYN and a talk that she gives on HPV vaccine. They 

find it to be very useful not only to work together, but also to raise awareness among each 

other’s constituents about the importance of lifelong prevention activities, whether it is primary 

prevention with vaccination or secondary prevention through screening throughout a lifetime. 

Raising community-wide awareness through different advocacy groups is helping Tennessee, 

although the numbers do not quite yet show it.

Ms. Pellegrini noted that a few weeks back, she answered the phone and was very excited 

because it was NIS-Teen. At the end of the survey, she was invited to provide her pediatrician’s 

name and address. She was told that, if authorized, they would check her parental recall 

against her children’s actual records. She wondered what percentage of respondents authorize 

that check with their pediatricians, what type of concordance they see between the records of 

parental recall, and what is done when there are differences.

Dr. Reagan-Steiner replied that approximately 70% of parents who complete the household

interview provide consent to contact their vaccination providers for records. All vaccination 

coverage estimates are based solely on provider-reported vaccination history, given that 

previous analyses have shown that there was discordance between parent recall and provider 

report.

Carol Hayes (ACNM) asked whether any attempt has been made to work directly with Title X 

programs. In the majority of states, the funds are allocated to FQHCs and sometimes other 

entities.

Dr. Curtis replied that from a broad perspective, FQHCs and community health centers were 

identified as stakeholders explicitly in the FOA. Most of the awardees have been working with 

those partners. The work that is occurring is primarily in local and state jurisdictions, and they 

have been encouraged to build ties there. FQHCs and community health centers have been 

extremely strong partners with some of the awardees.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

69 

Update on HPV Vaccine Safety

Dr. Lakshmi Sukumaran

Immunization Safety Office

Centers for Disease Control and Prevention

Dr. Sukumaran provided a brief background; reviewed HPV vaccine safety publications, which 

have predominantly been in quadrivalent HPV vaccine; discussed current HPV vaccine safety 

related activities at CDC; and discussed plans for 9vHPV vaccine safety monitoring. Three HPV 

vaccines are currently available, including: 1) 4vHPV (GARDASIL®), which was licensed in 

2006 and of which 80 million doses have been distributed1,2; 2) 2vHPV (CERVARIX®), which 

was licensed in 2009 and of which 839,600 doses distributed1,3; and 3) 9vHPV (GARDASIL®9), 

which was licensed in 2014 and of which 5 million doses distributed1,2 [1Doses distributed in the 

US through September 2015; 2Kuter B, personal communication, 20 October 2015; and 3Tofa A, 

personal communication, 14 October 2015].

There are three components to CDC’s vaccine safety monitoring infrastructure, including the 

following: 1) VAERS, the frontline spontaneous reporting system to detect potential vaccine 

safety issues; 2) VSD, a large linked database system used for active surveillance and 

research; and 3) Clinical Immunization Safety Assessment Project (CISA), an expert 

collaboration that conducts individual clinical vaccine safety assessments and clinical research.

Regarding post-licensure HPV vaccine safety studies starting with quadrivalent vaccine and 

general safety, a VAERS post-licensure safety summary showed that the proportion of reports 

for venous thromboembolism (VTE) and syncope after quadrivalent vaccine were higher than 

expected1. Updated VAERS reviews were published in 2013 and 2014, and no new concerns 

were identified2,3. The VSD conducted near real time monitoring following over 600,000 

quadrivalent vaccine doses and found no associations with the listed outcomes4. However, 

there was a non-significant elevated risk for VTE in females 9 through 17 years5. A general 

safety assessment from two large US health plans with almost 190,000 female vaccinees found 

that 4vHPV was associated with syncope on the day of vaccination and skin infections in the

two weeks following vaccination6. [1 Slade et al, Postlicensure safety surveillance for 

quadrivalent human papillomavirus recombinant vaccine. JAMA 2009; 2 Stokley et al, Human 

Papillomavirus vaccination coverage among adolescent girls, 2007-12, and postlicensure 

vaccine safety monitoring 2006-2013 – United States. MMWR 2013; 3 Stokley et al, Human 

Papillomavirus vaccination coverage among adolescents 2007-13 and postlicensure vaccine 

safety monitoring 2006-2014 – United States. MMWR 2014; 4 Gee et al, Monitoring the safety 

of quadrivalent human papillomavirus vaccine: findings from the Vaccine Safety Datalink. 

Vaccine 2011; 5 Relative risk calculated using Poisson based maximized sequential probability 

ratio test (maxSRPT); and 6 Klein et al, Safety of quadrivalent human papillomavirus vaccine 

administered routinely to females, Arch Ped Adolesc Med 2012].

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

70 

Because the VAERS study showed an increased proportion of reports of VTE and the VSD 

study showed a non-significant elevated risk in VTE following HPV vaccine, further studies 

evaluating VTE were conducted. In two national register-based cohort studies, no elevated risk 

for VTE was found following HPV vaccine. In addition, a VSD study using self-controlled case 

series method found no increased risk of VTE following quadrivalent vaccine in persons aged 9 

through 26 years [Arnheim-Dahlstrom et al, Autoimmune, neurological, and venous 

thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human 

papillomavirus vaccine in Denmark and Sweden: cohort study. BMJ 2013; Scheller et al, 

Quadrivalent human papillomavirus vaccine and the risk of venous thromboembolism. JAMA 

2014; and Naleway et al, Absence of venous thromboembolism risk following quadrivalent 

human papillomavirus vaccination, Vaccine Safety Datalink, 2008-2011. Vaccine (in press)].

Because Guillain-Barré Syndrome (GBS) is a rare outcome following immunization, the VSD 

extended surveillance for GBS from the previously mentioned study. The VSD did not observe 

an increased risk of GBS following quadrivalent vaccine among females ages 9 through 26 

years. The surveillance period was 6 years, and over 1.4 million doses of quadrivalent vaccine 

were administered. After electronic data and medical records were reviewed, there were 0 

incident cases of GBS within 42 days following quadrivalent vaccine.

There have also been concerns for potential associations with autoimmune and neurologic 

disease following 4vHPV. No evidence for a causal association has been observed between 

4vHPV and autoimmune and neurologic conditions in 4 large epidemiologic studies. The first 

study examined 16 autoimmune conditions; the second study assessed 23 autoimmune and 5 

neurologic conditions; the third study assessed 6 autoimmune conditions; and the last study 

considered multiple sclerosis and demyelinating diseases [1Chao et al, Surveillance of 

autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. J 

Intern Med 2012; 2Arnheim-Dahlstrom et al, Autoimmune, neurological, and venous 

thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human 

papillomavirus vaccine in Denmark and Sweden: cohort study. BMJ 2013; 3Grimaldi-Bensouda 

et al, Autoimmune disorders and quadrivalent human papillomavirus vaccination of young 

female subjects. J Intern Med 2013; and 4Scheller et al, Quadrivalent HPV vaccination and the 

risk of multiple sclerosis and other demyelinating diseases of the central nervous system. 

JAMA 2015].

In terms of the safety of HPV vaccines in pregnancy, there have been studies of both 

quadrivalent and bivalent vaccines. For 4vHPV, there was no increased risk of fetal loss, 

spontaneous abortion, or congenital anomalies in Phase III clinical trials1. In addition, the 

4vHPV pregnancy registry identified no concerns [1Garland et al. Pregnancy and infant 

outcomes in the clinical trials of a human papillomavirus type 6/11/16/18 vaccine: a combined 

analysis of five randomized controlled trials. Obstetrics & Gynecology 2009; and 2Goss et al. 

Final report on exposure during pregnancy from a pregnancy registry for quadrivalent human 

papillomavirus vaccine. Vaccine 2015].

For 2vHPVin pregnancies, although there was no overall increased risk of adverse pregnancy 

outcomes in pre-clinical trials, pooled analyses of these trials have shown a possible increased 

risk of spontaneous abortion in women 15 through 25 years of age who were vaccinated around 

the last menstrual period (LMP)1,2. However, a post-licensure study found no evidence of 

increased risk of spontaneous abortion or other adverse pregnancy outcomes in women 

inadvertently vaccinated around LMP3 [1Descamps et al. Safety of human papillomavirus 

(HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: A pooled analysis of 11 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

71 

clinical trials. Human Vaccines 2009; 2Wacholder et al. Risk of miscarriage with bivalent 

vaccine against human papillomavirus (HPV) types 16 and 18: pooled analysis of two 

randomised controlled trials. BMJ 2010; and 3Baril et al. Risk of spontaneous abortion and other 

pregnancy outcomes in 15-25 year old women exposed to human papillomavirus-16/18 AS04-

adjuvanted vaccine in the United Kingdom. Vaccine 2015].

In a review of the findings from a 2011 Institute of Medicine (IOM) report on AEs of vaccines 

with regard to HPV vaccine, for the outcome of syncope, the IOM concluded that “the injection 

of a vaccine was a contributing cause of syncope.” This could be any injected vaccine and is 

not specific to HPV. For the outcome of anaphylaxis, the IOM concluded that “the evidence 

favors acceptance of a causal relationship between HPV vaccine and anaphylaxis.” Again, this 

is similar to other vaccines [Adverse Effects of Vaccines: Evidence and Causality, Institute of 

Medicine, Aug 2011; http://www.iom.edu/Reports/2011/Adverse-Effects-of-Vaccines-Evidenceand-Causality.aspx]. For example, a recent VSD study (McNeil) showed that anaphylaxis after 

vaccination occurred at a rate of 1.31/million vaccine doses. In this study, rates of anaphylaxis 

following HPV vaccine were similar to other vaccines.

Pertaining to some recent concerns in HPV vaccine safety, case reports in the media of Primary 

Ovarian Insufficiency (POI) following HPV vaccine led to public concern. Cases reported to 

VAERS were reviewed, and there were no safety findings1. Complex Regional Pain Syndrome 

(CRPS) is a syndrome of chronic pain and autonomic changes in extremity that can sometimes 

occur after trauma. Case reports in Japan of pain following HPV vaccination led to suspension 

of their HPV vaccine recommendation due to concerns of CRPS. Case reports were reviewed 

and adjudicated, and there was no evidence for a causal association observed between bivalent 

vaccine and CRPS2. In addition, there were no safety findings in VAERS. For Postural 

Orthostatic Tachycardia Syndrome (POTS), concerns in Europe lead to an EMA review of 

POTS and CRPS following vaccination3. This review is ongoing and the EMA has not 

recommended any change in vaccination [1http://www.cdc.gov/vaccinesafety/vaccines/hpv/hpvsafety-faqs.html; 2Huygen et al. Investigating Reports of Complex Regional Pain Syndrome: An 

Analysis of HPV-16/18-Adjuvanted Vaccine Post-Licensure Data. EBioMedicine 2015; and 3 

http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2015/07/WC50018948

1.pdf].

Regarding current HPV vaccine safety related activities at CDC, within VAERS there is ongoing 

monitoring of US reports, clinical reviews of deaths and other pre-specified AE outcomes as 

needed (for example, there is an ongoing review of POTS following HPV vaccine), and FDA 

collaboration with CDC on HPV monitoring. Within CISA, there is a study assessing the 

feasibility and impact of implementing an oral water hydration strategy prior to vaccination to 

prevent post-vaccination pre-syncope and syncope in adolescents and young adults. There is 

also a POTS technical review that will be done in response to the spontaneous reports and 

public concern. Within VSD, there is a study addressing quadrivalent vaccine safety following 

inadvertent exposure during pregnancy. In addition, there are studies addressing safety 

concerns from case reports and/or the media including a study of the long-term risk of 

autoimmune disease following quadrivalent vaccine; POI following 4vHPV; and mortality 

following 4vHPV and other adolescent vaccines. The study of mortality following vaccination 

showed no increased risk of death during the 30 days after immunization.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

72 

With respect to 9vHPV safety, among seven pre-licensure studies1,2, 9vHPV was found to be 

generally well-tolerated in over 15,000 subjects. The AE profile was similar to that of 4vHPV; 

however, there was more injection site swelling and erythema in the 9vHPV group. Among 

inadvertent pregnancies occurring during the clinical studies3, the proportion of adverse 

outcomes observed was consistent with those observed in the general population. A post hoc 

analysis showed that pregnancies within 30 days of 9vHPV vaccination resulted in a 

spontaneous abortion more frequently than after 4vHPV. The rate was 27.4% in the 9vHPV 

group compared to 12.7% in the quadrivalent group. Both rates are within the spontaneous 

abortion background rates, which range from 10% to 31%4,5 [1http://www.fda.gov/downloads/ 

BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM426457.pdf; 2https://clinicaltrials.gov/ 

ct2/show/NCT01651949?term=v503&rank=3; 39vHPV is FDA Category B for pregnancy; 4Gray 

RH, Wu LY. Subfertility and risk of spontaneous abortion. Am J Public Health 2000; 5Wilcox A et 

al. Incidence of early loss of pregnancy. NEJM 1988].

For 9vHPV safety monitoring and evaluation at CDC, in VAERS there will be monitoring of US 

reports, clinical reviews of pre-specified outcomes as needed, and the FDA will be collaborating 

with CDC on 9vHPV monitoring. This table shows preliminary data from VAERS 9vHPV 

vaccine reports as of October 2, 2015. During this time period, 5 million doses of GARDASIL®9 

had been distributed through September 2015 in the US. VAERS received 193 reports, with an 

age range from 5 through 72 years with a median of 14 years. The onset interval ranged from 0 

to 20 days with a median of 0. There were 8 serious reports and 0 deaths. The most common 

terms found in reports were “no adverse event” in 52 reports, dizziness in 27 reports, and 

syncope in 25 reports. No AE is reported when there is a vaccination error without an AE, such 

as administration of the vaccine outside the recommended age range. In addition, there have 

been no new data mining findings for 9vHPV vaccine.

In VSD, there is near real time monitoring for several pre-specified outcomes through Rapid 

Cycle Analysis (RCA). The outcomes are similar to those evaluated in the original VSD study 

and include anaphylaxis, allergic reactions, appendicitis, GBS, seizure, stroke, syncope, VTE, 

pancreatitis, and injection site reaction. There will also be an epidemiologic study evaluating 

spontaneous abortion following inadvertent 9vHPV administration.

There are also 9vHPV post-marketing commitments to be conducted by the manufacturer 

including: 1) completion of two 10-year study extensions evaluating long-term safety, 

immunogenicity, and effectiveness in the licensed groups; 2) an observational study to further 

characterize the safety profile in 10,000 persons; and 3) a pregnancy registry of exposures 

occurring within 30 days prior to the last menstrual period or any time during pregnancy. FDA’s 

sentinel initiative will be conducting a general safety study and a pregnancy outcomes study.

In conclusion, a large body of published and preliminary data from many sources demonstrate 

the safety of HPV vaccines. Safety monitoring and evaluation will continue for all HPV vaccines 

with enhanced monitoring for 9vHPV during the initial uptake phase.

Discussion Points

Regarding the series of studies that found no association between vaccination and the 

outcomes of interest, Dr. Duchin (NACCHO) said it would be very helpful to include the strength 

of association being rejected through a study. He can say that he has found no associations in 

his personal experience as well, which is not very meaningful. A study that is meaningful should 

include some measure of the level of risk being excluded.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

73 

Dr. Moore noticed that in the VAERS reporting, there was a very wide age range of 5 through 72 

years of age. She asked whether there was any qualitative or significant and important 

difference in the nature of AEs reported among the ages for whom the vaccine is recommended 

as opposed to those for whom it was obviously administered but not recommended.

Dr. Sukumaran replied that these data are all preliminary, but most of the reports outside of the 

recommended age range were the “no AE” reports. The median age was 14 years, so the 

majority of reports were within or close to the recommended age range. There was no 

difference.

Dr. Plotkin (Vaccine Consultant) thought there was an important international aspect of this. 

Considering that this vaccine was invented by a US government laboratory, the US has some 

responsibility with regard to the use of the vaccine elsewhere. The Japanese withdrawal of 

government support for HPV vaccine was mentioned during this presentation. Recently, a 

French study was published that in effect blamed the vaccine for causing GBS. He strongly 

recommended that CDC publish a supplement in the MMWR on the safety of HPV, consider 

publishing a supplement in Clinical Infectious Diseases (CID) of all safety studies published, or 

at least publish a summary article in a journal with a large circulation in order to inform foreign 

users of HPV about the safety data from the US where the vaccine has been used in millions of 

individuals.

Dr. Sukumaran responded that there is currently an overview paper of the HPV vaccine safety 

studies that is almost complete.

Monitoring Impact of the HPV Vaccination Program / HPV Vaccine WG Plans

Lauri Markowitz, MD

HPV Vaccine Working Group

National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention

Centers for Disease Control and Prevention

Dr. Markowitz briefly presented data on the impact of the HPV vaccination program in the US. 

Post-licensure monitoring is important to evaluate the real world effectiveness of HPV vaccines. 

Because the impact of HPV vaccines on cancers, the main target of vaccination programs, will 

not be observed for decades, more proximal outcomes are being evaluated. Population impact 

on early and mid HPV-related outcomes has been reported now from a variety of countries. 

These outcomes include prevalent HPV infection, genital warts, and cervical pre-cancer lesions.

This year, a review and meta-analysis of population level impact and herd effects following HPV 

vaccination programs was published. This was a review of 20 studies in 9 high-income 

countries conducted within four years of vaccine introduction. Among the findings were that in 

countries with 50% or greater coverage, among females younger than age 20, HPV 16/18 

prevalence decreased by at least 60%. In countries using quadrivalent vaccine, anogenital 

warts decreased by about 60%. There was evidence of herd effects, including decreases in 

anogenital warts among older females and in males. There was some evidence of cross 

protection against other types. In countries with less than 50% coverage, there were also early 

but smaller decreases in prevalence and anogenital warts. There were no significant increases 

in non-vaccine types [Drolet et al. Lancet Infect Dis 2015;15:565-80].

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

74 

Some of the first post-licensure vaccine impact data were reported from Australia, where high 

coverage was achieved through school-based vaccination programs in the target age groups 

and in catch-up age groups. As noted, a rapid decrease in genital warts was observed soon 

after vaccine introduction among females less than 21 years of age and 22 through 30 years of 

age. While the vaccination program was only targeting females during this time, a decline was 

also observed among heterosexual males less than 21 years of age and 21 through 30 years of 

age [Ali et al. BMJ 2013].

Although there are substantial international data, Dr. Markowitz focused on US data during this 

session. Impact monitoring in the US is being conducted evaluating HPV prevalence, genital 

warts, cervical pre-cancers, and cancers in a variety of settings. In terms of prevalence, vaccine 

types in self-collected vaginal swabs in National Health and Nutrition Examination Survey 

(NHANES), data ACIP has seen before, show a decline in prevalence of types targeted by the 

quadrivalent HPV vaccine. As noted, there was a 56% decline in 6,11,16,18 prevalence among 

all 14 through 19 year olds in the first four years of the vaccination program, while no decline 

was observed in other age groups. Of note, there was no reported decline in sexual behavior or 

declines in other categories of HPV types between the two time periods. Data from further 

years of NHANES data will be available soon [Markowitz et al. JID 2013;208:385-93].

More recently, impact on prevalence among women in their 20s has been demonstrated. A 

study by Dunne et al evaluated HPV prevalence among women age 20 through 29 years of age 

who were undergoing cervical screening in an integrated health care system in the Northwest. 

Residual cervical specimens were tested for HPV in 2007, 2012, and 2013. Of the subjects, 

21% had received 3 doses and 32% had received at least one dose. Prevalence of 6,11,16,18 

deceased between these two time periods from 10.6% to 6.2%, which is a 40% decline. In 

2012-2013, vaccine type prevalence was 3.2% among those had received at least 1 dose and 

7.6 among those who were unvaccinated. In multi-variable analyses controlling for race, age, 

and markers of sexual activity, having received 3 doses before 19 years of age was highly 

protective, with an adjusted prevalence ratio of 0.1 [Dunne et al. JID 2015].

Data for genital warts are available from MarketScan® commercial claims and encounters 

database for 2003 through 2010. The main finding is the decline in genital warts prevalence 

among females aged 15 through 19 from 2.9/1000 persons-years in 2006 to 1.8/1000 personsyears in 2010. In women aged 20 through 24 and 25 through 29, prevalence increased or 

remained level through 2009 and decreased in 2010. Among males, prevalence increased 

initially or was stable during most of this time period and there was no decrease in 15 through 

19 year olds. [Flagg et al. AJPH 2013;103:1428–35]. Data from MarketScan® are being further 

evaluated now. The early decrease in 15 through 19 year old females is consistent with the 

decline in vaccine type HPV prevalence seen in NHANES during this time period 

There are a variety of challenges in monitoring HPV vaccine impact on cervical lesions. First, 

these lesions are detected through cervical cancer screening and there have been changes in 

screening recommendations. In 2009, ACOG recommended to start screening at age 21 rather 

than within 3 years of onset of sexual activity, and less frequent screenings in older age groups. 

In 2012, multiple advisory groups made similar recommendations. Also, there are no national 

cervical cancer screening registries and there are incomplete linkages with vaccination 

registries.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

75 

In spite of these limitations, an ongoing CDC project is assessing cervical cancer precursor 

lesions and associated types in five catchment areas. This project, HPV IMPACT, capitalized 

on the infrastructure of the EIP. The project collects data on CIN2+, cervical intraepithelial 

neoplasia grade 2 or worse, and adenocarcinoma in situ in women 18 years and older. HPV 

types are determined in a subset of women 18 through 39 years of age, and there is a search 

for vaccine history. Each site also collects data to estimate population level cervical cancer 

screening annually in the catchment area.

In terms of incidence rates of CIN2+ by age group and by site in 2008 and 2012 and the percent 

change between these years, among 18 through 20 year olds the incidence dropped 82% to 

94%. This cannot be attributed primarily to vaccine as screening dropped dramatically as well 

during this time period. In 21 through 29 year olds, there were significant declines in CIN2+ in 

Connecticut and New York, but not in California or Oregon. In the oldest group, 30 through 39 

year olds, little difference is observed in any of the sites.

In three IMPACT sites (New York, Oregon, California), trends in CIN2+ incidence per 100,000 

and percent screened by age and year were evaluated. In all sites there was clearly a decline 

in screening in the youngest age group and declines in CIN2+. This suggests that the declines 

in lesions in the youngest age group are primarily due to decreases in detection through 

screening. However, the declines in CIN2+ exceeded declines in screening by 5% in New York, 

7% in California, and 15% in Oregon in this age group. Among women 21 through 29 years of 

age, screening rates also decreased, but to a smaller degree. CIN2+ decreased in New York, 

but not in Oregon or California. There were inconsistent changes in screening and CIN2+ rates 

in the oldest age group. These data illustrate the challenges in assessing vaccine impact at this 

time due to changes in screening practices. The reductions in lesions in 18 through 20 year 

olds and the more variable declines in 20 through 29 year olds are largely due to concurrent 

decreases in screening. Further work is ongoing to investigate the contribution of vaccination.

Although there are challenges in determining impact due to vaccination in terms of overall 

incidence of CIN lesions, evaluation of HPV type-specific CIN lesions provides some clearer 

evidence. Regarding HPV 16/18 associated CIN2+ among women eligible for vaccination, by 

year and vaccination status, there is a linear decline of the percent of lesions associated with 

vaccine type HPV among vaccinated women from 55% in 2008 to 29% in 2012. There was no 

change in the percent of lesions due to 16/18 among the unvaccinated or among those with 

unknown vaccine status.

In this same study, using the indirect cohort method, vaccine effectiveness was estimated by 

looking at HPV types in vaccinated and unvaccinated cases. This analysis evaluated the 

percentage of CIN2+ attributable to HPV 16/18 by timing of vaccination in relation to the 

abnormal cervical cancer screening test which led to the CIN diagnosis. Increasing time 

between vaccination and screening test increases the likelihood that vaccination occurred 

before infection with the type causing the pre-cancer lesion. Vaccine effectiveness would be 

expected to increase with increases in this interval. The percent of lesions in unvaccinated 

women due to 16/18 was 53.6%. In those vaccinated before the screening test, the percent 

attributed to 16/18 decreased from 50% to 13% with increasing interval. The adjusted 

prevalence ratio was significant for those vaccinated 25 months or more before the screening 

test. For those vaccinated 48 months or more before the abnormal test, the adjusted prevalence 

ratio was .28 for an estimated VE of 72%.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

76 

This same analysis was repeated limited to the highest grade lesions of CIN3 or worse, lesions 

which are more likely to progress to cancer. There are fewer cases of CIN3 than CIN2+. The 

prevalence of 16/18 was higher in these lesions, but the findings were very similar. Again, the 

percent attributable to HPV 16/18 decreased with increasing time between vaccination and the 

screening test from 80% to 40%, and the adjusted prevalence ratio was significant for those 

vaccinated 37 to 48 months before screening test [Hariri et al. Cancer 2015;121:2775-81].

A variety of other studies are ongoing, including an evaluation of prevalence among MSM, 

further analyses using administrative data, and vaccine effectiveness studies by number of 

doses.

In summary, available data from the US and other developed countries show early impact of 

HPV vaccine on HPV prevalence and other early HPV-associated outcomes. As expected, the 

first US impact observed was on HPV prevalence and genital warts among females 14 through 

19 years of age and later among those in their 20s. There are challenges in evaluating vaccine 

impact on incidence of cervical pre-cancers in the US, but available data suggest early impact. 

Further data are forthcoming on vaccine impact and vaccine effectiveness. Achieving higher 

vaccine coverage will lead to greater impact of the vaccination program.

As a reminder, 9vHPV was licensed by the FDA in December 2014 and was recommended by 

ACIP in February 2015. An MMWR Policy Note was published in March 2015. The vaccine 

became available through the VFC program in April 2015. By September 2015, 94% of CDC’s 

64 awardees had placed orders for this vaccine. In September 2015, 36% ordered 9vHPV only. 

Over 85% of managed care plans decided to cover 9vHPV. As of September 2015, 5 million 

doses have been distributed in the US.

Future ACIP HPV Vaccines WG plans are to review data on reduced dose schedules, including 

a 9vHPV 2- vs 3-dose immunogenicity trial, other immunogenicity data, post-licensure 

effectiveness studies, and cost-effectiveness analyses. The WG plans to present reduced dose 

data to ACIP starting in February 2016, so the HPV Vaccine WG’s work with ACIP over the next 

year is anticipated to be focused on this topic.

 

Discussion Points

Dr. Susan Lett (CSTE) requested clarification about the effectiveness data that are expected to 

be available comparing 2 versus 3 doses.

Dr. Markowitz replied that one problem with assessing the effectiveness of 2 versus 3 doses is 

that most people who have received only 2 doses did not receive the doses in a 0,6 month 

interval but rather started the 0,2,6 month schedule and did not receive the third dose. 

Therefore, the effectiveness data might not inform the 2-dose schedule being evaluated in the 

immunogenicity trials, in which there is a longer interval between the 2 doses.

Dr. Stephens asked whether there are any data or any plans to assess head and neck cancers 

associated with HPV and the impact of the vaccine.

Dr. Markowitz replied that this has been challenging because there is no precursor lesion for the 

oral pharyngeal cancers. This has been an impediment to conducting a trial to assess the 

efficacy of the vaccine on these cancers. This has been the topic of a lot of discussion. There 

are some data from a post hoc analysis from a trial in Costa Rica to evaluate the impact of the 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

77 

vaccine on prevalence of oral infection. The entire topic of HPV-related oral pharyngeal cancers 

and head and neck cancers were reviewed with ACIP in the past in preparation of making an 

HPV recommendation. Impact on oral HPV prevalence could be evaluated in some studies.

Regarding reduction of HPV 16/18 associated CIN2+ among women whose vaccination status 

is unknown with vaccination defined as 1 or more doses, Dr. Strikas asked Dr. Markowitz to 

comment on what proportion of the women had fewer than 3 doses.

Dr. Markowitz did not have these data with her, but thought it was fairly comparable to US data 

in which approximately 70% of people who have initiated the series have received all 3 doses.

Dr. David Kimberlin (AAP) asked whether any comments could be made about efforts to monitor 

for juvenile onset of laryngeal papillomatosis. 

Dr. Markowitz indicated that a system has been initiated to collect data on recurrent respiratory 

papillomatosis through a network of pediatric ear, nose, and throat (ENT) providers. That was 

just set up in 2015, and CDC hopes to have data from this prospectively and retrospectively.

It was unclear to Dr. Walt Orenstein (NVAC) whether the data presented for the indirect cohort 

was with the full 3 doses, or if it was 1 or more doses. The numbers seemed to be inconsistent 

with the pre-licensure trials for at least the 3-dose series, which seemed to have far higher 

estimates of effectiveness.

Dr. Markowitz replied that this was for at least 1 dose, and that CDC is in the process of 

performing this analysis to assess 2 versus 3 doses. She would say it is not that inconsistent 

with the pre-licensure trials, because many of these people would have been vaccinated after 

infection, even with the longer interval between vaccination and screening test that led to 

detection of the lesion. The very high efficacy found in the pre-licensure trials is from the per 

protocol population, comprised of those people who were sero- and PCR-negative at the time of 

vaccination.

Introduction

Lorry Rubin, MD

ACIP, Workgroup Chair 

Dr. Rubin reminded everyone that inactivated Vero cell culture-derived Japanese encephalitis 

(JE) vaccine (JE-VC; IXIARO®) is the only JE vaccine available in the US. JE-VC is 

manufactured by Valneva, formerly Intercell. Inactivated mouse brain–derived JE vaccine (JEMB; JE-VAX®) is no longer available in the US.

In terms of how ACIP recommendations for the use of JE-VC have evolved, in 2009 the FDA 

licensed JE-VC for use in adults and ACIP approved recommendations for a primary series in 

adults. In 2010, the MMWR Recommendations and Reports from 1993 were updated. In 2011, 

ACIP approved recommendations for use of a booster dose in adults based on new information 

Japanese Encephalitis Vaccine

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

78 

and published a Policy Note in the MMWR. In 2013, ACIP approved recommendations for use 

of a primary series in children and published an additional Policy Note in the MMWR. 

The JE Vaccine WG’s current objectives are to: 1) review newly available safety and 

immunogenicity data for JE-VC; 2) review epidemiology and risk of JE in travelers; 3) review 

ACIP recommendations for use of JE vaccine in consideration of updated safety, 

immunogenicity, and traveler risk data; and 4) update the MMWR Recommendations and 

Reports published in 2010. 

Presentations during this session pertained to the change in the JE vaccine distributor, 

immunogenicity in adults ≥65 years of age, an accelerated dosing schedule, concomitant 

administration with rabies vaccine, and the JE Vaccine WG’s summary and plans.

New Clinical Data for IXIARO®

Dr. Katrin Dubischar

Senior Scientist, Clinical Research

Valneva Austria GmbH

During this session, Dr. Dubischar discussed the change in the IXIARO® distributor for the US, 

immunogenicity of IXIARO® in older adults, and results of a clinical trial investigating an 

accelerated dosing schedule for IXIARO® and concomitant administration with rabies vaccine. 

Novartis Vaccines was the US distributor of IXIARO® from FDA approval in 2009 to February 

2015. In March 2015, GSK acquired US distribution rights to IXIARO® as part of a multi-product 

transaction with Novartis. In June 2015, Valneva announced termination of the marketing and 

distribution agreement for IXIARO® with GSK. Valneva plans to handle these commercial 

activities on its own and with already established vaccine distributors and wholesalers. The 

transition from GSK to Valneva is anticipated to be completed by year-end 2015. Both GSK and 

Valneva are fully committed to a smooth transition to ensure continuous supply of IXIARO® to 

patients and customers, and ongoing access to medical affairs and pharmacovigilance for 

IXIARO®. 

Regarding immunogenicity of IXIARO® in adults aged ≥65 years, clinical trial IC51-315 was 

conducted as part of a post-marketing commitment with the US FDA to determine the safety 

and immunogenicity of the vaccine in an elderly population. Subjects with stable underlying 

conditions such as hypercholesterolemia, hypertension, cardiovascular disease (CVD), or non 

insulin-dependent diabetes mellitus (DM) were included. This was an open-label, single arm 

study in which IXIARO® was administered using the standard dose and schedule of 0.5 ml

administered intramuscularly (IM) on Days 0 and 28. The study cohort size was 200 subjects. 

The study included two follow-up visits, one on Day 70 to determine safety and for serology 

assessments and one at Month 7 via telephone. The population was enrolled from five trial 

sites in Germany and Austria. The primary endpoints of the study were rate of serious adverse 

events (SAEs) and medically attended AEs until Day 70. The main secondary endpoints 

included the rate of subjects with SAEs and medically attended AEs until Month 7, unsolicited 

AEs until Day 70 and Month 7, solicited AEs 7 days after each dose, and immunogenicity at Day 

70 as determined by GMTs and seroconversion rates (SCRs). SCR was defined as subjects 

who had a 50% plaque reduction neutralization test (PRNT50) titer of > 1:10. This neutralizing 

antibody titer is widely accepted as protective.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

79 

On day 70, 65% of the 197 adults aged ≥65 years had a PRNT50 titer ≥1:10 and the GMT was 

37. The results from this study were compared with a SCR of 96% and GMT of 240 in younger 

adults in the pivotal licensure trial. Stratified by age, the data were further assessed to 

understand whether an advanced age of 75 years and older would have an additional impact on 

immunogenicity. There was no significant difference in SCRs and GMTs in those aged 65 

through 74 years and those aged ≥75 years.

In conclusion, similar to other vaccines, IXIARO® shows lower SCRs and GMTs in elderly 

compared to younger adults. Advanced age of ≥75 years (range 75 through 83) has no further 

impact on GMTs and SCRs. No long-term data were gathered in this population. Duration of 

protection is thus uncertain, especially as immune response to the primary series is low. Elderly 

individuals may benefit from a booster before further exposure to JE virus.

Regarding an accelerated dosing schedule for IXIARO® and concomitant administration with 

rabies vaccine, Dr. Dubischar first provided some background from a study published by CDC 

authors on use of JE vaccine among US travelers. This study was conducted at Global

TravEpiNet sites. Global TravEpiNet is a CDC-sponsored consortium of US clinical practices 

that provide pre-travel care. The study period was from September 2009 to August 2012, in a 

period after the licensure of IXIARO®. The travelers in the study were classified based on their 

itineraries as either high-risk or lower-risk travelers, and one factor that was addressed was to 

determine days to departure at which travelers visited the travel clinic. Only 50% of travelers at 

higher risk for JE presented in time for the FDA-approved, two-dose (Days 0 and 28) schedule 

of IXIARO®. 

Novartis Vaccines, which was the distribution partner of IXIARO® at the time, sponsored and 

conducted the clinical study to test an accelerated schedule. However, the serological testing 

for the study was done by Valneva so the study has the same immunogenicity assessments as 

studies conducted through the trial program for this vaccine. The study was an observerblinded, randomized, Phase III study in adults 18 through 65 years of age. There were four 

study groups. The first group consisted of 167 subjects who received the JE and rabies 

vaccines according to conventional administration schedules. Specifically, IXIARO® was 

administered on Days 0 and 28, and the rabies vaccine Rabipur® (identical to the US-licensed 

Rabavert®) was administered on Days 0, 7, and 28. Placebo administrations were given to 

obscure the treatment groups. The second group of 217 subjects received the accelerated 

schedules for both of the vaccines, with IXIARO® administered on Days 0 and 7, and Rabipur®

administered on Days 0, 3, and 7. The third group of 221 subjects received Rabipur® alone 

administered according to its conventional schedule on Days 0, 7, and 28. The fourth group of 

56 subjects received IXIARO® alone administered according to the conventional schedule on 

Days 0 and 28. Study follow-up was performed on Days 7 and 28 post-dose 2 of JE-VC for all 

study groups, and at 6 and 12 months after initiation of the series. In addition, the group who 

received the accelerated schedule had further visits to determine immune kinetics.

One of the study objectives was to assess non-inferiority of the accelerated schedule compared 

to the standard schedule as measured by SCR 28 days after the last active immunization. The 

groups that were compared were those who received an accelerated schedule of JE vaccine 

administered concomitantly with rabies vaccine versus those who received JE vaccine alone in 

a conventional schedule. The margin to accept non-inferiority was set to 10%, meaning that the 

accelerated schedule was considered non-inferior to the conventional schedule if the lower 

bound of the two-sided 97.5% CI of the difference in the percentages of subjects with PRNT50

titer ≥1:10 measured 28 days after last active vaccine administration was greater than 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

80 

-10%. A second study objective was to determine if the concomitant administration of JE plus 

rabies vaccines has an impact on the immunogenicity of the JE vaccine. Here the test was for 

non-inferiority of the GMTs 28 days after the last active immunization comparing the group who 

received a conventional schedule of both vaccines versus the group who received the 

conventional schedule of the JE vaccine alone. The margin was a GMT ratio of 0.5. Pertaining 

to demographic data for the study population, the mean age was in the high 30s for all three 

groups who received the JE vaccine and the gender ratio was fairly well-balanced.

With respect to the results for the primary non-inferiority tests, on Day 0 the seropositive rate 

was about 6% for the groups receiving the accelerated JE and rabies schedules and about 9% 

in the group who received JE vaccine alone. At 28 days after the second dose of JE-VC, the 

accelerated schedule resulted in 99% seroconversion and the conventional schedule resulted in 

100% seroconversion. Thus, non-inferiority was clearly demonstrated. In terms of the kinetics 

of the SCR, the onset of the immune response was rapid for subjects administered JE vaccine 

in an accelerated schedule with a SCR of 99% on Day 14, 7 days after the last active dose, 

The SCR remained at high levels throughout the 12-month study observation period.

 

Also, the accelerated JE vaccine schedule resulted in higher GMTs, with about a 3-fold higher 

maximum GMT compared to the conventional schedule. The titers peaked at a level of 1,255 

on Day 21, which is 14 days after the second immunization. Furthermore the GMTs with the

accelerated schedule remained higher than the titers observed with the standard schedule.

The group receiving concomitant JE vaccine and rabies vaccine had a GMT of 291 at 28 days 

after the last active dose compared to a GMT of 331 in the group receiving just the conventional 

schedule of the JE vaccine alone, resulting in a GMT ratio of 0.88 indicating non-inferiority. In 

terms of kinetics in the two groups, for all time points for which immunogenicity of JE vaccine 

was assessed, the titers were fairly comparable.

Safety data are shown in the following table, with the rates being fairly comparable for all of 

these measures between the three study groups described here: 

R/JE-Conv

N=166

n (%)

R/JE-Acc

N=217

n (%)

JE-Conv

N=56

n (%)

Any AE (Solicited and 

Unsolicited) 140 (84) 191 (88) 49 (88)

Solicited AEs 137 (83) 185 (85) 44 (79)

Unsolicited AEs 69 (42) 108 (50) 29 (52)

Severe Related 

Unsolicited AEs 2 (1) 4 (2) 1 (2)

Related SAEs 0 (0) 0 (0) 1 (2)

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

81 

One AE was thought to be possibly related to vaccination. This was a case of moderate eyelid 

edema that affected both eyes and a generalized pruritus that occurred on the day of 

vaccination. The subject had a complete recovery without medical treatment. The doctor who 

reported the event thought it was a medically important condition and did not further vaccinate 

the subject. Because there was no hospitalization and the event was not life-threatening, it did 

not fulfill the more stringent SAE criteria.

In terms of the solicited AEs within 7 days after any dose, the vaccine safety profile was 

generally similar across the groups. Local solicited reactions were reported by 63% to 75% of 

subjects across groups, and systemic solicited reactions were observed in 54% to 66%. As a 

reminder, solicited local AEs included erythema, induration, and pain. The predominant 

symptom was pain. Again, the rates are fairly comparable between the group receiving 

accelerated schedules of IXIARO® and Rabipur® and the group receiving the conventional 

vaccine schedules. They appear somewhat lower for the group who received just the JE 

vaccine. It is important to note that the two groups receiving IXIARO® and Rabipur® had 

vaccine administered during at least 3 of 4 study visits, while the group receiving IXIARO® alone 

had active immunizations administered during only two visits and the rest were placebo 

injections. Solicited systemic AEs included loss of appetite, nausea, fatigue, myalgia, arthralgia, 

and headache. The most common reactions were myalgia, headache, and fatigue. 

In conclusion, the licensed immunization schedule for IXIARO® consists of two doses, 4 weeks 

apart. A high number of international travelers present too close to departure to complete this 

primary immunization schedule1. JE vaccine, administered according to an accelerated dosing 

schedule with a one-week interval between the 2 doses, induced short-term immune responses 

which were non-inferior to those obtained following the licensed immunization schedule2. This 

accelerated dosing schedule is not approved in the US. The accelerated dosing schedule 

resulted in titers that were consistently higher than with the conventional schedule both midterm (6 months) and long-term (1 year)3. Both immunogenicity and safety results supported 

concomitant administration of JE and rabies vaccines, according to both the accelerated and 

conventional schedules [1Deshpande et al. Use of Japanese Encephalitis Vaccine in US Travel 

Medicine Practices in Global TravEpiNet. Am J Trop Med Hyg 2014;91:694; 2Jelinek T et al. J 

Travel Med 2015;22:225; 3Cramer et al. Abstract LB-3134, presented at 63rd Annual Meeting 

ASTMH, New Orleans, USA, November 2014].

Regarding regulatory review and updates to IXIARO® labelling, a use in elderly update to the 

European labelling was approved in April 2015. The recommendation contained there is as 

follows: 

“As with many vaccines, the immune response in older persons (≥65 years of age) to 

IXIARO is lower than in younger adults. Duration of protection is uncertain in older 

persons, therefore a booster dose (third dose) should be considered before any further 

exposure to JE virus.”

An accelerated dosing schedule was approved in Europe in April 2015. The recommendation 

reads as follows:

 

“Persons aged 18-65 years can be vaccinated in a rapid schedule as follows: First dose 

at Day 0. Second dose: 7 days after first dose.” 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

82 

- The European recommendation to administer a booster dose of IXIARO after 12 

months if risk for JE exposure persists, remains unchanged. 

With respect to the US, Valneva currently is exploring possible approaches to update the 

IXIARO® Prescribing Information with these and other new clinical data, and continues to work 

with FDA on respective plans. However, any FDA approved updates to the Prescribing 

Information for IXIARO would be unlikely to occur before 2017. 

Discussion Points

Dr. Belongia requested that Dr. Dubischar elaborate on the approval by the European 

Medicines Agency (EMA) in Europe, plans with the FDA, and whether the regulatory 

requirements/expectations differ for EMA versus FDA in terms of the timing of one versus the 

other.

Dr. Dubischar explained that the scrutiny of the EU is comparable, but the efforts and number of

documents that need to be provided and compiled for filing in the US are different from the 

filings in Europe. European variation of that type is a relatively short few-month process, and 

the European regulators require a study report. In contrast, filing with the FDA is a more 

complicated endeavor and is associated with significantly higher costs. In addition to study 

reports, it is expected that a study database and all programs to analyze that database are 

submitted to the FDA. The study was sponsored by Novartis, and Valneva is working with 

Novartis, now GSK, to obtain these additional files.

Regarding rates of AEs that occurred with the vaccines, Dr. Romero inquired as to whether 

there were any differences in the severity of the reactions.

Dr. Dubischar responded that there were not. In general, the majority of the reactions were mild 

and there was no difference in the rates for moderate or severe reactions between the study 

groups.

Dr. Karron wondered if anything was known about the number of travelers in the US over the 

age of 65 who are getting a primary series, how long they would stay in an area, and how many 

would be returning such that they might need a booster dose. In addition, she asked whether 

anyone could comment about protective levels of neutralizing antibody against JE.

Regarding the estimated rates of US travelers and their travel patterns, Dr. Dubischar deferred 

to Dr. Hills. In terms of the neutralizing antibody levels that would be considered a protective 

titer, the definition used for seroconversion in the Valneva trials was a neutralizing antibody titer 

of ≥1:10. It is not clear if a titer below that would also be protective but ≥1:10 is the measure 

that is accepted by WHO and is the licensure criterion used with FDA.

Dr. Hills replied that for US travelers, CDC has information on doses distributed but does not 

have information on doses administered nor a breakdown by age group.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

83 

JE Vaccine WG Summary and Plans

Dr. Susan Hills

Medical Epidemiologist

National Center for Emerging and Zoonotic Infectious Diseases

Centers for Disease Control and Prevention

Dr. Hills presented on behalf of the JE Vaccine WG a summary of the new safety, 

immunogenicity, and other data presented during this session. She also discussed plans and 

the timeline for presentation and discussion of additional data and topics.

As a reminder, when the JE Vaccine WG was reformed in March 2015, its objectives were to: 

1) review newly available safety and immunogenicity data for JE-VC; 2) review updated data on 

the epidemiology and risk of JE in travelers; 3) review ACIP recommendations for use of JE 

vaccine in consideration of updated safety, immunogenicity, and traveler risk data; and 4) 

prepare a revised MMWR Recommendations and Reports to update the document that was 

published in 2010. 

The data on JE-VC immunogenicity in adults ≥65 years of age were presented earlier by Dr. 

Dubischar. In summary, there has been one observational study in adults aged ≥65 years. At 

42 days after the second dose, 65% (128/197) of older adults were seroprotected and the 

neutralizing antibody GMT was 37. In comparison, in the previous pivotal licensure study in 

younger adults, at 28 days after the second dose 96% (352/365) of subjects were seroprotected

and the neutralizing antibody GMT was 243. 

The WG reviewed and discussed these data, and its assessment and summary of JE-VC 

immunogenicity in adults aged ≥65 years was that: 1) there are lower seroprotection rates and 

GMTs following the 2-dose primary series in adults aged ≥65 years compared to younger 

adults; 2) there are no data on safety, immunogenicity, or optimal timing of a possible third

primary series or early booster dose; and 3) the data have been submitted to FDA, but no 

change is expected in the recommended dosing schedule for adults aged ≥65 years due to the 

lack of data on the safety, immunogenicity, or optimal timing of a possible third primary series or 

early booster dose. 

Following this review, two options were considered by the WG. The first was an off-label 

recommendation for a third primary series dose or early booster dose for adults 65 years of age

and older before further exposure to JE virus. The second was no off-label recommendation, 

but incorporation of the data into the updated MMWR Recommendations & Reports document

to make the information available for vaccine providers. The WG concluded that the data were 

not sufficient to support an off-label recommendation. The plan is to incorporate the data into

the updated MMWR Recommendations & Reports document. The issue will be reevaluated if 

new data become available. 

The second topic presented by Dr. Dubischar was the use of JE-VC in an accelerated primary 

series of 2 doses administered 7 days apart in adults aged 18 through 65 years. In summary, 

the study showed that the accelerated primary series was not inferior to the conventional dosing 

schedule of 2 doses administered 28 days apart. In the accelerated schedule group, 99% 

(203/206) of subjects were seroprotected after 2 doses administered 7 days apart. In the 

comparison standard primary series group, 100% (49/49) of subjects were seroprotected after 2 

doses administered 28 days apart. 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

84 

The WG reviewed and discussed these data. Their assessment and summary of the topic of an 

accelerated primary series of JE-VC was that: 1) there are limited safety and immunogenicity 

data in approximately 200 adults with a 2-dose primary series administered 7 days apart; 2) 

there are no data in children aged <18 years or in adults aged >65 years; and 3) the data have 

not been submitted to FDA and it is not known if or when this will occur. 

Again, two options were considered by the WG. The first was an off-label recommendation for 

an accelerated primary series of 2 JE-VC doses administered 7 days apart in adults aged 18

through 65 years. The second was no off-label recommendation, but incorporation of the data 

into the updated MMWR Recommendations & Reports document. The WG concluded that the 

data are promising for use of an accelerated 2-dose primary series, but should be submitted for 

FDA review. No off-label recommendation is requested by the WG. The WG plans to 

incorporate the data into the updated MMWR Recommendations & Reports document.

In addition to the data presented during this session, additional new JE-VC safety and

immunogenicity data are available. The WG plans to present these new data during the ACIP 

meeting in February 2016. These include data on the duration of protection following the 

primary series and a booster dose in adults, duration of protection and booster doses in 

children, and updated post-licensure safety data. The remaining three ACIP JE Vaccine WG 

objectives will be addressed during the ACIP meeting in June 2016. These include a review of 

the epidemiology and risk of JE in travelers; a review of the ACIP recommendations for use of 

JE vaccine in consideration of updated safety, immunogenicity, and traveler data; and a 

presentation of a draft of the updated MMWR Recommendations & Reports document.

The key components to be updated in the MMWR Recommendations & Reports document 

include the following:

 Removing the mouse brain-derived JE vaccine information and recommendations as this 

vaccine is no longer available in the US

 Incorporating recommendations for the JE-VC pediatric primary series and for a booster 

dose in adults, previously published as MMWR Policy Notes

 Updating the epidemiology and risk of JE in travelers 

 Including new information on the JE-VC distributor and the new safety, immunogenicity, coadministration, and dosing schedule data

Discussion Points

Dr. Sun (FDA) commented on the issue of labeling changes in Europe versus the US. The 

issue is fairly complex because of the different approaches to the review of data by the FDA 

compared to other national regulatory agencies. Based on that, companies develop their 

strategy for submission. In terms of approvals, the FDA does not accept data from trials on face 

value. Instead, the agency also requests raw data and tries to reproduce the conclusions and 

findings through its own analyses, which is a fairly long and more rigorous process. In addition, 

the FDA performs pre-approval inspections of clinical trial sites and manufacturing facilities, 

especially if there are any concerns. All of this taken together makes this a rigorous but long 

and arduous process.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

85 

It occurred to Dr. Strikas that the data from the study of the Global TravEpiNet sites conducted 

by CDC in which an estimate was made of people at lower- and higher-risk of JE could be 

combined with airline data and/or National Health Interview Survey (NHIS) data, which used to 

ask people where they were traveling and if they had traveled to certain parts of the world in the 

past, to develop some semblance of a denominator of people at some degree of risk of JE. He 

asked if this had been done or contemplated.

Dr. Fischer responded that a previous study was published of an airport survey that assessed 

the proportion of travelers taking direct flights from the US to Asia that were at higher risk based 

on ACIP criteria. Those data were not broken down by age group, because there was no 

concern at that point regarding older age. The proportion of those people who had received JE 

vaccine was then determined. That study was conducted prior to licensure of IXIARO®, so the 

proportions are not directly relevant. The TravEpiNet study was conducted among all travel 

medicine clinics. The proportion of travelers who attend travel medicine clinics to get JE vaccine 

is not known. It is different from yellow fever vaccine which requires a certificate for travel, so 

the representativeness of those travelers is unknown. There likely would be data available by 

age group in that study, but he did not have those results.

 

Introduction

Arthur Reingold, MD

University of California, Berkeley

Chair, ACIP Combination Vaccine Work Group

Dr. Reingold reminded everyone that the ACIP Combination Vaccines WG was formed in 

February 2015 to review published and unpublished data related to the safety and 

immunogenicity of two new combination vaccines: 1) Quadracel® DTaP-IPV vaccine for 

children 4 through 6 years of age; and 2) an investigational hexavalent (HV) pediatric vaccine

(DTaP5-IPV-Hib-HepB), which is a 3-dose series for children at 2, 4, and 6 months of age.

The WG’s Terms of Reference for Quadracel® Vaccine have been satisfied with the 

presentation of safety and immunogenicity data to the ACIP in June 2015, followed by the 

publication of the Policy Note in the MMWR on September 4, 2015. During the July 

Combination Vaccines WG conference call, safety and immunogenicity data were presented by 

Sanofi Pasteur and Merck for the investigational HV pediatric vaccine. This is an interesting 

vaccine in that it is a joint venture of two different vaccine manufacturers, Sanofi Pasteur and 

Merck, who have come together to combine their respective products into a single vaccine.

The investigational pediatric HV vaccine includes antigens for diphtheria, tetanus, pertussis, and 

polio from Sanofi Pasteur and antigens for Hib and hepatitis B from Merck. There are licensed 

vaccines containing the same antigens. Although PedvaxHIB® contains 7.5 μg of 

polyribosylribitol phosphate polysaccharide linked to outer membrane protein complex (PRPOMPC), the HV vaccine contains 3 μg. Recombivax HB® contains 5 μg of hepatitis B surface 

antigen (HBsAG), but the HV vaccine contains 10 μg. 

Combination Vaccines

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

86 

The BLA was accepted by FDA for review in October 2014. The proposed indication is for a 3-

dose series in children from 6 weeks through 4 years of age administered at 2, 4, and 6 months 

of age. Based on the materials reviewed, no safety or immunogenicity concerns were identified 

by the WG. This session focused on the safety and immunogenicity of the investigational 

pediatric HV vaccine. 

Immunogenicity and Safety of DTaP5-IPV-Hib-HepB:

A Pediatric Hexavalent Combination Vaccine

Andrew W. Lee, MD

Director, Vaccines Clinical Research

Merck Research Laboratories

Dr. Lee thanked the WG for their helpful discussions to date and ACIP for the opportunity to 

speak during this session. On behalf of Sanofi Pasteur and Merck, he presented an overview of 

MCM Vaccine Co. (a partnership between Merck & Co., Inc. and Sanofi Pasteur Inc.), as well as 

the pediatric HV vaccine composition; Study 005 design and immunogenicity results; Study 006 

design and immunogenicity results; and integrated safety results for DTaP5-IPV-Hib-HepB. 

Because the safety design was very similar across Study 005 and 006, it was possible to 

integrate the safety results across the two studies.

Merck and Sanofi Pasteur formed a partnership called the MCM Vaccine Co. in 1991 to develop 

this combination vaccine. The work related to the development and manufacturing of the 

vaccine was divided as equally as possible. Merck contributes the HepB and Hib components 

and Sanofi Pasteur contributes DTaP5 and IPV, and they are also responsible for the 

formulation and release of the product. In terms of development, Merck is the clinical lead and 

Sanofi Pasteur is the regulatory lead. Both companies will co-promote the product once it is 

approved. Merck is the lead for pharmacovigilance and holds the global safety database.

In terms of the composition of the HV vaccine, the components come from the licensed 

vaccines as depicted in the following table:

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

87 

With the combination vaccine schedule being 3 doses at 2, 4, and 6 months, there is an 

additional dose as compared to the two infant dose schedules for the PEDVAX HIB® product. 

This permitted the exploration of lower amounts of the Hib antigen as compared to the amount 

contained in PEDVAX HIB®. Based on the results of a Phase II study that assessed several 

formulations of the HV vaccine and the level associated with long-term protection of ≥1.0 μg/mL

from Hib disease and geometric mean concentrations (GMCs), the PRP-OMPC-containing 

formulations of the HV had acceptable Hib responses; whereas, the PRP-T formulation did not. 

While both the HV PRP-OMPC 3 μg and 6 μg formulations had similarly high Hib responses, the 

6 μg formulation was associated with slightly higher rates of injection-site and systemic AEs. 

On balance, HV PRP-OMPC 3 μg was chosen for further development [Diaz-Mitoma et al. 

Vaccine 29 (2011) 1324–1331]. Diaz-Mitoma et al. Vaccine 29 (2011) 1324–1331].

The following is a table of the US combination vaccine schedules, which indicates how many 

shots are associated with each regimen: 

For the HV vaccine, there are two options for completing the HV regimen at the toddler time 

point of 15 to 18 months of age. Either 1 injection of Pentacel® or Daptacel® plus the 

monovalent Hib, resulting in a total of 4 or 5 injections for the HV regimen. There is also 

variation in the number of injections associated with the Pediarix® regimen. Depending upon 

which Hib vaccine is used, there are either 2 or 3 infant doses, which results in either 7 or 8 total 

injections for that regimen. Overall, the HV regimen has 2 to 4 less injections than the Pediarix®

+ Hib regimen, depending upon the monovalent Hib used. The HV regimen has 1 to 2 less 

injections than Pentacel® + HepB, depending upon which vaccines are used for the toddler

dose.

Regarding Study 005, the pivotal non-inferiority US study, HV immunogenicity was compared to 

the licensed component control. Most of the immunogenicity endpoints were after the third dose 

at 7 months. There also were some primary pertussis endpoints after the toddler dose due to 

the need for 4 doses for the pertussis vaccination series. After the third dose, immunogenicity 

was also evaluated for concomitantly administered RotaTeq® vaccine [Marshall et al. Pediatrics 

136 (2015) e323-332].

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

88 

The primary endpoints for Study 005, most of which pertained to the non-inferiority measures, 

included the following:

 Non-inferiority of antibody response rates to all HV antigens at one month Post-Dose 3 

in HV versus control vaccine recipients

 Non-inferiority of pertussis antibody GMCs at one month Post-Dose 3 and at one month 

Post-Toddler Dose in recipients of HV versus control vaccine infant doses

 Acceptably high polio antibody titers at one month Post-Dose 3 in HV recipients

The secondary endpoints for Study 005, which related to different ways of measuring the Hib 

and concomitant responses, included the following:

 Non-inferiority of proportion of HV versus control vaccine recipients with PRP 

concentrations ≥0.15 μg/mL at one month Post-Dose 3

 Non-inferiority of PRP GMCs at one month Post-Dose 3 in HV versus control vaccine 

recipients

 Non-inferiority of anti-rotavirus immunoglobulin A (IgA) GMCs at one month Post-Dose 3 

in HV versus control vaccine recipients

In general, the antibody response rates after the third dose were overlapping with the exception 

of the Hib responses at the two different thresholds when the responses appear to be higher for 

the HV regimen as compared to the control. This is consistent with the monovalent Hib 

literature that shows that the PRP-OMPC type of Hib vaccine has more rapid development of 

immune responses as compared to the PRP conjugated to tetanus toxoid (PRP-T)-based Hib 

vaccines. Otherwise, most of the antigens appear to be quite similar. Post-Dose 3 noninferiority criteria were met for all pertussis antibody endpoints except filamentous hemagglutinin 

(FHA) GMC. However, for the same antigen, the response rate criteria were met for FHA. The 

confidence intervals were largely overlapping for the Post-Toddler dose, and all of the noninferiority criteria were met for all pertussis antibody endpoints. Following Dose 3, rotavirus 

immunogenicity was non-inferior when given concomitantly with hexavalent or control vaccines. 

Again, the confidence intervals were overlapping. Thus, non-inferiority criteria were met 

whether measured by the percent of 3-fold increase or GMCs.

With respect to Study 006, the lot consistency study, was designed using three consecutive lots 

of the HV vaccine to account for the larger number of subjects who actually received HV. There 

is a control arm of a smaller size as well. Given that consistent immune responses to all 

antigens were demonstrated across all three lots, it was possible to combine the 

immunogenicity results for the three lots. Immunogenicity was also evaluated for concomitant 

administration of Prevnar 13® after the third dose in this study.

The results for Study 006 were very similar to those for Study 005 after the third dose in that all 

non-inferiority criteria were met except for the GMC measure of FHA. There was one difference 

in Study 006 versus Study 005 in the Post-Toddler dose in that the criteria for the GMC 

measure of the PRN pertussis antigen were narrowly missed. The non-inferiority criteria 

required that the lower bound exceed 0.67, which was missed. Regarding the antipneumococcal (PN) responses one month Post-Dose 3, the non-inferiority criteria were met for 

12 of the 13 serotypes contained in the vaccine. For serotype 6B, the non-inferiority response

was missed for the study endpoint but would have satisfied the Prevnar 13® non-inferiority 

criterion used for licensure, which required that the lower bound of the GMC ratio exceed 0.5. 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

89 

As noted previously, safety measurements for US studies 005 and 006 were integrated across 

studies. Daily temperature measurements were taken for 5 days after each vaccination. The 

day of vaccination counted as Day 1. The ratings for mild, moderate, and severe are standard 

and are shown as follows in Centigrade and Fahrenheit: 

38.0 ≤ Mild ≤ 38.4°C 100.4 ≤ Mild ≤ 101.1°F

38.5 ≤ Moderate ≤ 39.4°C 101.3 ≤ Moderate ≤ 102.9°F

Severe ≥ 39.5°C Severe ≥ 103.1°F

For 5 days after each vaccination, systemic AEs were solicited for fever, vomiting, crying 

abnormally, drowsiness, appetite loss, and irritability. Solicited injection-site AEs included 

redness, swelling, and pain/tenderness. Unsolicited AEs were monitored for 15 days after each 

vaccination. SAEs were collected for 6 months after the infant vaccination series and for 15 

days after the toddler vaccinations (which was not the HV vaccine). Deaths and vaccine-related 

SAEs at any time during the study were also collected. In terms of the percent of participants 

with any solicited injection-site AEs on Day 1 through Day 5 following any infant vaccination, the 

incidences appear to be quite similar. In general, solicited systemic AEs during the first 5 days 

following any infant dose also were quite similar across the different categories. However, there 

was an increased incidence of pyrexia for the total HV as compared to the control.

Further assessment of temperature data for the first 5 days following any infant dose showed 

that there was about a 13% higher incidence of subjects with any fever ≥ 38.0°C among HV 

recipients versus controls. The confidence intervals do not cross zero for mild and moderate; 

however, they do cross zero for severe temperature. Thus, there is no significant difference in 

severe temperature elevations, though there was for mild and moderate temperature elevations. 

Data not shown during this session but collected during the study showed that the vast majority 

of temperature elevations were 2 days or less in duration, as would be expected for an 

inactivated or subunit vaccine. Regarding participants with fever ≥ 38°C by dose for Days 1 

through 5, there is less of a separation between HV and control fever rates after the first dose 

and more of a separation after the second and third doses. There also appears to be a plateau 

between Doses 2 and 3 in fever rates for the HV vaccine.

With the increase in fever rates, care was taken to monitor for fever-related medical events. 

There was a low and similar incidence of pyrexia SAEs in the HV group as compared to the 

control group. In addition, there were no febrile seizures or seizures within 15 days of any 

vaccination. When the safety monitoring period was extended to 180 days following the infant 

doses, some cases of febrile seizures and seizures were identified in both vaccination groups. 

However, these cases were quite distant from vaccination, and none of the cases were 

considered related to vaccination.

There was a low incidence of vaccine-related SAEs and study discontinuations due to AEs in 

both vaccination groups. The statistical analysis showed that there was no statistical difference 

between the HV group compared to the control group. None of the deaths that occurred during 

the study were considered to be vaccine-related. It is important to keep in mind that the ratio of 

HV to control subjects is approximately 4:1.

In summary, the pediatric HV vaccine is an investigational product that is under review by the 

FDA. A decision is anticipated from the FDA before the end of 2015. The data shown during 

this session demonstrated robust immunogenicity and an acceptable safety profile in rigorous 

Phase III studies with a total of over 4,250 infants. The infant series immune responses were 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

90 

non-inferior to control, except for the GMC of FHA. However, FHA response rates were noninferior. An increase was observed in self-limited, mild-to-moderate fever, but this was not 

associated with significant increases in clinical consequences. The concomitant rotavirus and 

pneumococcal conjugate vaccine immunogenicity was similar when given with HV or control. 

Combination vaccines improve vaccination compliance and timeliness. Overall, this DTaP5-

IPV-Hib-HepB pediatric vaccine will provide a new option for meeting the recommended US 

vaccination schedule with fewer injections. 

Discussion Points

In terms of there being no difference in the clinical consequence of fever between the two 

groups, Dr. Rubin wondered whether there was a difference in the necessity to go to the doctor 

or ED for evaluation or for admission to the hospital due to fever even if patients ultimately did 

well.

Dr. Lee replied that this is covered under the incidence of SAEs, and there was a small 

difference. There were three cases of SAEs of fever that required either hospitalization or ED 

visits. Given the ratio of HV to control subjects, this incidence does not represent a significant 

difference.

Dr. Bolongia asked whether there is any information about the expected cost of the vaccine 

once it is approved relative to the current vaccines.

Dr. Lee responded that he was unable to comment on the price of the vaccine at this time. The 

price of the vaccine will be announced once licensure is obtained.

Ms. Finley (AIM) noticed that the HepB amount is a higher dose, yet an increased percentage of 

children are receiving the birth dose. She requested an explanation for why a higher dose of 

HepB would be included.

Dr. Lee explained that the dose as compared to the monovalent pediatric dose of HepB was 

based on the potential for immune interference between the HepB responses and the other 

components of the vaccine. Similar to what was shown for Hib, various doses of HepB were 

evaluated in the Phase II studies. The 10 μg was optimal for immunogenicity and safety overall.

Dr. Sawyer (PIDS) asked whether this vaccine is the same as the one currently used in Canada, 

or if it has a different composition. If it is the same, he wondered how many doses have been 

given.

Dr. Lee replied that the Canadian formulation is different. The HV used in Europe is Infanrix®

Hexa. There are differences primarily in the Hib component. DTaP5-IPV-Hib-HepB has a PRPOMPC Hib component, while Infanrix® Hexa contains a PRP-T. The other difference is that 

DTaP5-IPV-Hib-HepB contains 5 antigens in the pertussis component of the vaccine, while 

Infanrix® Hexa has 3 antigens.

Dr. Walter asked whether there was an increase in antipyretic use among the subjects who had 

fever.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

91 

Dr. Lee responded that the study protocol included an instruction not to give antipyretics prior to 

the appearance of fever, given the paper from The Lancet showing that there could be blunting 

of immune response. However, antipyretic use was permitted in response to fever. There was 

a slightly higher rate of antipyretic use of 61% in the HV group compared to 57% in the control 

group. This was thought to be consistent with the slightly higher rates of fever observed.

From a consumer perspective, Ms. Pellegrini expressed gratitude on behalf of small children 

everywhere. Combination vaccines reduce the burden on families. This is not only about fewer 

needlesticks, but also is about improving compliance.

Introduction

Arthur Reingold, MD

University of California, Berkeley

Chair, ACIP Cholera Vaccine Work Group

Dr. Reingold indicated that the ACIP Cholera Vaccine WG is a new WG, which is anticipated to 

have a relatively short lifespan. No cholera vaccine is currently licensed in the US. CVD 103-

HgR is an oral cholera vaccine that is anticipated to be licensed in the US in 2016. The ACIP 

Cholera Vaccine WG was created to review the evidence for use of CVD 103-HgR in US adult 

travelers. The WG’s specific Terms of Reference are to:

 Review data on safety, immunogenicity, and efficacy for CVD 103-HgR vaccine 

(PXVX0200)

 Propose ACIP recommendations for use of CVD 103-HgR in US adult travelers and 

publish approved recommendations in MMWR Recommendations and Reports

Regarding the timeline, PaxVax filed a BLA with the FDA with a request for priority review. The 

FDA review is anticipated to be completed by June 2016. The plan is to call for an ACIP vote 

on recommendations for use of CVD 103-HgR as soon as possible after the vaccine is licensed.

Cholera in US Travelers

Karen K. Wong, MD, MPH

Medical Officer

Division of Foodborne, Waterborne, and Environmental Diseases

National Center for Emerging and Zoonotic Infectious Diseases

Centers for Disease Control and Prevention

Dr. Wong presented an overview of cholera in the US. Cholera is caused by gram-negative, 

rod-shaped, toxigenic Vibrio cholera (V. cholera) O1, which accounts for over 99% of global 

cases, or O139. Cholera causes a watery diarrhea that may be severe and rapidly fatal without 

proper treatment. Cholera is endemic in over 50 countries, and it may also cause epidemics. It 

is estimated to cause 3 to 5 million cases of illness and 100,000 to 130,000 deaths annually. 

Cholera Vaccine

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

92 

Countries reporting cholera deaths and imported cases to the WHO in 2014 are depicted in the 

following map, followed by a specific list:

World Health Organization Weekly epidemiological record. 2 Oct 2015. No. 40, 2015, 90, 517–544. 

http://www.who.int/wer/2015/wer9040.pdf?ua=1

The shaded blue countries located in Africa, Asia, and the Island of Hispaniola in the Caribbean 

are areas where cholera deaths have been reported. The black dots mark the countries that 

have reported imported cholera cases.

Deaths were reported by 24 countries in:

 Africa (1,882)

 Asia (42)

 Caribbean [Hispaniola] (307)

Imported cases were reported by 11 countries: 

 Australia (2)

 Canada (2)

 Chile (1)

 France (1)

 Germany (1)

 Japan (5)

 Malaysia (33)

 Russia (1)

 Singapore (2)

 United Kingdom (14)

 United States (7)

V. cholerae is classified by its O-antigen structure. More than 200 O serogroups have been 

identified. The WHO defines cholera as illness caused by toxigenic O1 and O139 because they 

have caused cholera epidemics. O1 can have two biotypes (El Tor and classical), as well as 

two serotypes (Inaba and Ogawa). V. cholerae colonizes the small intestine and produces 

cholera toxin. Cholera toxin is comprised of an A subunit that causes secretory diarrhea, as 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

93 

well as five identical B subunits that surround the A subunit and bind the toxin to cell membrane 

receptors. 

Cholera is easily transmitted by water and food contaminated by human feces or environmental 

reservoirs. It grows rapidly in warm, moist, non-acidic foods. It is a fragile organism that does 

not tolerate drying, acidity, or sunlight. Cholera attaches to copepods or zooplankton, which can 

be consumed with contaminated water or food. The incubation period of cholera ranges from 

hours to about five days, and the duration of illness ranges from one to a few days. Secondary 

cases are rare if sanitation is adequate. 

The clinical presentation of cholera ranges from no apparent symptoms to severe hypovolemic 

shock, also known as cholera gravis. The risk factors for cholera gravis include high-dose 

exposure; low gastric acidity such as occurs with gastrectomy or antacid therapy; blood group 

O, the prevalence of which is approximately 45% in the US; and other strain and population 

factors [Harris JB et al. Blood group, immunity, and risk of infection with Vibrio cholerae in an 

area of endemicity. Infect Immun. 2005 Nov;73(11):7422-7; http://www.redcrossblood.org/learnabout-blood/blood-facts-and-statistics].

Cholera gravis causes a profuse watery diarrhea, which can be one or more liters per hour. It 

typically causes something called “rice-water stools” named for its appearance of being flecked 

with mucus and epithelial cells. Vomiting and leg cramps may also be part of the clinical 

presentation. Cholera can cause severe dehydration characterized by loss of skin turgor, 

hypotension, weak pulse, and altered mental status. It can be rapidly fatal if untreated. A 

descriptive account of cholera in an American physician was published in 1971. The timeline 

and symptoms described here are typical of severe cholera:

Diagnosis of cholera is made by bacterial culture of a rectal swab or stool specimen. However, 

under-diagnosis is common because special transport media and culture media are needed to 

isolate the organism. Serologic diagnosis may also be made using acute and convalescent 

vibriocidal titers. These antibodies typically increase two weeks after exposure and decrease 

two months after the illness. 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

94 

The mainstay of clinical management is supportive care. Oral and intravenous rehydration can 

reduce the fatality rate to less than 1%. Antimicrobial therapy may also be used in conjunction 

with hydration. It is recommended for severely ill patients and all hospitalized patients, and it 

reduces fluid loss, duration of illness, and duration of fecal carriage. Zinc supplementation in 

children reduces the duration of illness and the volume of diarrhea. 

Vibriocidal antibodies are the best marker for protection against V. cholerae infections. 

Lipopolysaccharide (LPS)-specific memory B cells may play a role in mediating long-term 

protection. Protection against cholera is serogroup-specific; that is, it protects against O1 or

O139, but it protects across the biotypes El Tor and Classical and the serotypes Inaba and

Ogawa. 

Cholera is very rare in the US and other countries with safe water and modern sanitation. There 

are few domestically acquired cases in the US, many of which are associated with Gulf Coast 

seafood consumption. Most US cases are associated with travel to cholera-endemic countries. 

Cholera is under-reported in the US, because testing for V. cholerae is not routine, and some 

cholera illnesses in travelers are not severe and may resemble other causes of traveler’s 

diarrhea. The following diagram shows the surveillance pyramid:

Beginning at the bottom of the pyramid, of all of the people who become ill, only a fraction seek

medical care. Of those, only some may have a diagnostic specimen submitted for testing. Only 

some of those specimens may be tested for cholera, which is not routine. Of those tested for 

cholera, not all will identify the pathogen. Thus, the cases that are confirmed and reported 

represent only the tip of the iceberg in terms of the true burden of illness.

With that in mind, there are some estimates of laboratory-confirmed cholera incidence in 

returning travelers. Among European and North American travelers to South America during 

the 1991 cholera epidemic, the incidence was estimated to be 0.3/100,000 people. Among 

Japanese travelers to Indonesia, the estimated incidence was higher at 13/100,000 people. 

Among all travelers returning from travel to the developing world who sought care at certain 

surveillance clinics from 1996 through 2004, the incidence was estimated at 5.8/100,000 

people. Note that the interpretation of these estimates should consider differences in the

surveillance methods. Surveillance of the European and North American travelers relied on 

passive reporting; whereas, surveillance of the Japanese travelers was somewhat enhanced as 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

95 

travelers were specifically tested for cholera infection [Wittlinger F et al. Risk of Cholera Among 

Western and Japanese Travelers. J Travel Med. 1995 Sep 1;2(3):154-158; Freedman DO et al. 

Spectrum of disease and relation to place of exposure among ill returned travelers. N Engl J 

Med. 2006 Jan 12;354(2):119-30]. 

There are also some estimates of laboratory-confirmed cholera incidence among persons 

traveling or living in cholera-affected areas. Among US citizens living in Peru the incidence of 

cholera was estimated to be 44/100,000 people per month of exposure from 1991 through 1993. 

Among US citizens providing medical services in Haiti during the cholera epidemic from 2010 to 

2011, the incidence was estimated at 321/100,000 people (1 of 311 study respondents reported 

receiving a diagnosis of cholera). Among travelers who sought care for diarrhea in multiple 

years between 1986 and 2011 during travel to Nepal, a cholera-affected country, zero cases of 

cholera were diagnosed. Cholera outbreaks have also been described among travelers. In 

Haiti in December 2010, a suspected cholera outbreak affected 10 of 14 French medical 

volunteers and 11 of 72 French military police engaged in response efforts and living in the 

same site [Taylor DN et al. Cholera among Americans living in Peru. Clin Infect Dis. 1996 

Jun;22(6):1108-9; Schilling KA et al. Diarrheal illness among US residents providing medical 

services in Haiti during the cholera epidemic, 2010 to 2011. J Travel Med. 2014 Jan-Feb;

21(1):55-7; Murphy H, Pandey P. Pathogens for travelers' diarrhea in Nepal and resistance 

patterns. Curr Infect Dis Rep. 2012 Jun;14(3):238-45; Haus-Cheymol R et al. A cluster of acute 

diarrhea suspected to be cholera in French travelers in Haiti, December 2010. J Travel Med. 

2012 May-Jun;19(3):189-91]. 

A cholera outbreak has also been described on a commercial airline flight. In 1992, a flight 

from Buenos Aires, Argentina stopped in Lima, Peru before landing in Los Angeles. A 

contaminated seafood salad was prepared in Lima and served to the flight passengers. Of the 

passengers, 100 of 194 tested had evidence of V. cholerae O1 infection. Of those, 75 had 

diarrhea that began a median 2 days after arrival, 10 patients were hospitalized, 1 patient died 

who was 70 years of age, and 19 of the cholera patients were US citizens [Eberhart-Phillips J et 

al. An outbreak of cholera from food served on an international aircraft. Epidemiol Infect. 1996, 

Feb;116(1):9-13]. 

A case series of surveillance data from 2001 through 2011 showed that 111 cholera cases were 

reported in US over an 11-year period. Of note, epidemic cholera began in Haiti in October 

2010. Of the cases over the study period, 46% were reported after the Haiti epidemic began. 

No secondary cases were reported in this series. Of the cases, 20 (18%) were domestically 

acquired and most of them reported seafood consumption. Of the cases, 90 (81%) were 

associated with international travel. The most common reason for travel was visiting friends and 

relatives (62%). Other reasons for travel included medical missions or other relief work (9%), 

tourism (7%), business (7%), and immigration to the US (5%). Of 87 travel-associated V. 

cholerae O1 cases, 74 (85%) had an isolate with a multidrug resistant pattern. Of the 111 

cases identified in this 11-year period, 108 were diagnosed by stool culture. Of those, 99% 

(n=107) were V. cholerae O1. Of the 107 V. cholerae O1, 22 (21%) were El Tor Inaba and 85 

(79%) were El Tor Ogawa. This graph shows the number of cholera cases by year and source 

from 2001 through 2011:

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

96 

Cases increased after 2010 due to travel to Hispaniola during a cholera outbreak, and these 

cases are shown in purple. Travel to other areas, shown in green, remains an important source 

of cholera cases. Domestically acquired cases along the Gulf Coast are shown in red 

[Loharikar A et al. Cholera in the United States, 2001-2011: a reflection of patterns of global 

epidemiology and travel. Epidemiol Infect. 2015 Mar;143(4):695-703]. 

More recently in 2012 to 2013, 30/32 (94%) patients with cholera reported in the US had 

traveled to a cholera-endemic area, including 18 from Haiti and 4 from the Dominican Republic. 

Unusually, there was 1 case in a healthcare worker with no travel exposure who cared for a 

cholera patient in the hospital. There was also 1 case in a person who reported exposure in a 

laboratory. The age of these patients ranged from 1 through 87 years. 

[http://www.cdc.gov/ncezid/dfwed/ pdfs/covis-annual-report-2012-508c.pdf. Accessed October 

8, 2015; http://www.cdc.gov/ncezid/dfwed/pdfs/covis-annual-report-2013-508c.pdf . Accessed 

October 8, 2015]. 

To summarize some of the key cholera features, severe cholera (cholera gravis) can be rapidly 

fatal if untreated. Cholera is often under-reported. Few cases are reported in the US, although 

incidence increased after the outbreak in Haiti began. Most cases in the US occur in persons 

who have recently traveled to cholera-affected areas. A few cases have been identified in 

healthcare workers and laboratory personnel providing medical services to cholera patients. 

Current CDC prevention recommendations for US travelers to cholera-affected areas center on 

safe food and water precautions and frequent handwashing. Chemoprophylaxis with antibiotics 

is not indicated. There is no vaccine recommendation, and no cholera vaccine is currently

licensed in the US. WHO prequalified vaccines, Dukoral® and ShancholTM, are mentioned as 

being available outside of the US [http://wwwnc.cdc.gov/travel/yellowbook/2016/infectiousdiseases-related-to-travel/cholera. Accessed October 8, 2015].

The current WHO recommendations for travelers to cholera-endemic areas state that:

The risk for most travelers is very low, even in countries where cholera epidemics occur, 

provided that simple precautions are taken. However, humanitarian relief workers in 

disaster areas and refugee camps may be at risk.

 

Consider for travelers at high risk:

• Killed oral O1 with whole-cell with B-subunit (Dukoral®) 

• Killed oral O1 and O139 (ShancholTM)

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

97 

On October 2, 2015, there was an announcement that a Strategic Advisory Group of Experts 

(SAGE) Working Group is forming to revise the WHO recommendations on oral cholera 

vaccines. 

As mentioned earlier, there is no cholera vaccine currently licensed in the US. However, there 

are two oral cholera vaccines available in other countries. ShancholTM is licensed in India and 

requires 2 oral doses spaced 2 to 6 weeks apart. Dukoral® is licensed in more than 60 

countries, primarily as a vaccine for travelers to cholera-endemic areas. In Sweden and 

Canada, it is also approved for traveler’s diarrhea prevention. It provides some short-term 

protection against enterotoxigenic E. coli (ETEC). It also requires 2 oral doses spaced 7 or 

more days apart, and requires a buffer solution. No country currently requires vaccination 

against cholera as a condition for entry. 

The vaccine the ACIP Cholera Vaccine WG is focused on is a different oral cholera vaccine 

known as CVD 103-HgR. Unlike the other two vaccines, CVD 103-HgR is a single dose, live 

attenuated oral cholera vaccine. CVD 103-HgR is soon to be under consideration for US 

travelers. It uses a recombinant V. cholerae O1, classical biotype, serotype Inaba. It confers 

protection against multiple biotypes and serotypes. Of the enzymatically active A subunit of 

toxin gene, 94% is deleted. The gene for the antigenic, non-toxic B subunit of the toxin is intact. 

The vaccine does not express enzymatically active cholera toxin, and it contains a marker to 

differentiate the vaccine strain from wild-type V. cholerae O1. This vaccine was previously 

licensed as Orochol® or Mutacol® and was used in non-US countries, including Switzerland, 

Canada, and Australia. Manufacture ceased for business reasons in 2004. In 2009, PaxVax 

acquired the licensure rights to redevelop CVD 103-HgR, or VaxchoraTM, for commercial use. 

They recently filed a BLA for use in adults travelers.

The ACIP Cholera Vaccine WG will review evidence for use of CVD 103-HgR and evaluate that 

evidence according to the GRADE framework. The WG hopes to inform recommendations for 

use of CVD 103-HgR in adult travelers in anticipation of the US licensure. In February 2016, the 

WG anticipates a presentation of the GRADE evaluation, as well as a presentation by the 

vaccine manufacturer. In June 2016, a presentation is anticipated of WG recommendations

regarding the use of this vaccine in adult travelers. 

Susan Goldstein, MD

National Center for Immunizations and Respiratory Diseases

On behalf of the STRIVE Team

Dr. Goldstein described the Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE), 

first recognizing the over 200 CDC staff who have participated in this trial within Sierra Leone 

and in Atlanta. In response to the West Africa Ebola outbreak that was unprecedented in size 

and complexity, WHO convened a consultation on potential Ebola therapies and vaccines in 

September 2014. One of the recommendations from the meeting was to “Accelerate [vaccine] 

development and safe use in countries with outbreaks.” With this recommendation noted and a 

large CDC presence in West Africa, CDC decided to expand the West Africa response to 

include a vaccine trial.

Ebola Vaccine Trial Update

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

98 

The overarching goal of STRIVE is to accelerate introduction and use of an Ebola prevention 

vaccine among at-risk people in Sierra Leone with concurrent evaluation of the efficacy and 

safety of the vaccine. The three primary objectives are to: 1) Estimate the efficacy of a single 

dose of vaccine in preventing laboratory-confirmed Ebola virus disease (EVD); 2) Assess SAEs 

following administration of the vaccine; and 3) Collect and store serum for baseline

seroprevalence and immunogenicity evaluations. STRIVE principal study partners include the 

College of Medicine and Allied Health Sciences (COMAHS) and the Ministry of Health and 

Sanitation (MOHS) in Sierra Leone; and CDC, the Biomedical Advanced Research and 

Development Authority (BARDA), and Merck/New Link Genetics in the US.

The vaccine, rVSV-ZEBOV, is a live-attenuated recombinant vesicular stomatitis virus (rVSV) 

vaccine that expresses the glycoprotein of the Kikwit strain of the Zaire Ebola virus (ZEBOV). 

The vaccine was developed by the Public Health Agency of Canada (PHAC), and Merck 

currently holds the license. rVSV-ZEBOV is administered as a single dose at a concentration of 

2 x 107 pfu/mL, and it is stored at -80oC.

STRIVE is an unblinded, randomized trial with phased enrollment over a period of 4 months. 

Participants are individually randomized to either the immediate group and are vaccinated at or 

within 7 days of enrollment, or the deferred group and are vaccinated 18 to 24 weeks after 

enrollment. There is no placebo. All participants will be vaccinated by the end of the study. 

Vaccine efficacy is measured by comparing EVD incidence in the vaccinated and deferred 

groups. AEs are assessed by following participants post-vaccination for 6 months. The study 

population is comprised of adults 18 years of age and older who are healthcare workers (HCW) 

in either an Ebola or non-Ebola facility. Being a healthcare worker is defined by working in a 

healthcare facility setting rather than by the specific job:

Physicians Laboratorians Cleaners

Nurses Pharmacists Administrators 

Health aids “Dressers” Security Guards

The study population also includes selected Ebola frontline workers: Surveillance Officers, 

Ambulance Drivers, Swabbers, and Burial Workers.

The study sites selected reflect the epidemiology of Ebola early in the course of the outbreak 

and the need for an appropriate sample size, which is a minimum of 6000 participants. Sites 

were also selected based on the logistical considerations of the existing infrastructure and the 

ability to enhance the infrastructure for buildings, cold chain, roads, and transportation. The 

ability to monitor for and ensure standard of care for AEs and EVD was also important. Work is 

performed in five districts, including Freetown, the country capital and urban center. There are 

7 vaccination sites, 3 data centers, 3 cold chain depots, and 1 laboratory. The main data hub 

and main vaccine depot are in Freetown. The following map shows the locations of the study 

sites, data centers, cold chain depots, and laboratory in Sierra Leone:

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

99 

Participants are monitored for AEs, SAEs, EVD, and pregnancy for 6 months post-vaccination. 

The deferred group is monitored from enrollment until vaccination and then for 6 months 

thereafter. Follow-up is done through monthly phone calls to each participant. If a participant 

cannot be contacted, there is a home visit. All SAEs are evaluated by one of the study 

physicians. Surveillance is also conducted to identify any participant who is admitted to an 

Ebola holding center, treatment center, or hospital isolation unit with suspect EVD.

Within the larger STRIVE study, there are two sub-studies for safety and immunogenicity. The 

safety sub-study is an intensive evaluation of safety and reactogenicity among over 400 initial 

participants, comprised of approximately 200 from the immediate group and 200 from the 

deferred group. These subjects filled out daily health cards for Day 1 through 28 for the 

immediate group after vaccination and the deferred group after enrollment. Follow-up was done 

by phone on Days 1, 3, 7, 14, and 28. The immunogenicity sub-study is being conducted in 

collaboration with Merck. The objective is to assess the baseline seroprevalence of Ebola and 

long-term immunogenicity after vaccination. Specimens are drawn at Time 0 (pre-vaccination) 

and at 1, 6, and 12 months post-vaccination. The specimens will be sent to the US and will be 

tested by Merck/Focus Diagnostics.

Enrollment is complete, with 8680 participants enrolled between April 9, 2015 and August 21, 

2015. As of October 18th, 5550 participants have been vaccinated. Of these, 4173 are in the 

immediate vaccination group and 1350 are in the deferred vaccination group. Deferred 

vaccination is ongoing. Deferred vaccination is planned to be finished by mid-December 2015.

The safety profile to date is consistent with other published studies. There have been no safety 

signals in sub-study and no vaccine-related SAEs. Of the 8 deaths reported to date among 

study participants, none was vaccine-related. In terms of surveillance, 43 participants have 

been evaluated for suspected EVD. All were EVD negative, 19 were found to be malaria 

positive by laboratory testing (RDT, ICT, smear), and 6 additional participants had clinicallydiagnosed malaria. Enrollment in the immunogenicity sub-study is complete with a total of 506 

subjects and 92% follow-up on eligible 1-month blood draws. The 6-month blood draws will 

commence in December 2015.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

100 

The interim results from the WHO Guinea Ring Vaccination Trial were published in The Lancet

on July 29, 2015. This trial utilizes a cluster-randomized ring vaccination with rVSV-ZEBOV 

around contacts and contacts of contacts of an index case. The vaccine is the Merck vaccine, 

which is the same vaccine used in the STRIVE trial. The rings are randomized to either

immediate vaccination or delayed vaccination, which is 21 days after randomization. The 

primary outcome of this study is laboratory-confirmed EVD 10 or more days after randomization. 

The interim analysis included 90 rings (48 immediate, 42 delayed). The authors concluded that 

VSV-ZEBOV “might be highly efficacious” and is “most likely effective at the population level 

when delivered during an EVD outbreak via a ring vaccination strategy.” Everyone is anxiously 

awaiting publication of the final results, which will have additional rings and probably more 

decisive conclusions [Henao-Restrepo AM. Lancet. 2015; 386: 857–866; Henao-Restrepo AM. 

BMJ. 2015:351].

Based on the interim results from Guinea, the WHO Ring Trial was expanded into Sierra Leone. 

There was no longer randomization, meaning that all rings are immediately vaccinated. To 

date, two rings have been vaccinated in Sierra Leone. The STRIVE protocol was amended to 

allow for early vaccination of deferred participants who have not yet been vaccinated if they are 

considered to be at higher risk of exposure to EVD. In early September 2015, an Ebola case 

was identified in a STRIVE study district. The case was treated in a peripheral health unit and 

an Ebola treatment unit where STRIVE participants worked and lived in a community where 

enrolled STRIVE participants lived. The amendment was activated and approximately 100 

deferred participants were vaccinated early.

Given the changing epidemiology of Ebola, with fewer and fewer reported Ebola cases in Sierra 

Leone, assessment of vaccine efficacy became unlikely. The low incidence of EVD meant that 

there was little likelihood of exposure among the study participants. Only 145 cases were 

reported in Sierra Leone since the study commenced, and few of these reported cases were 

among HCW. The expansion of the WHO Ring Trial into Sierra Leone further decreased the 

likelihood of exposure. However, STRIVE continues with the collection of important safety and 

immunogenicity data that will be used for licensure.

The following table summarizes the Phase I, II, and III Ebola trials currently ongoing in the three 

affected countries:

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

101 

The Merck and GSK vaccines are being used in most of the trials. Two trials were recently 

commenced in Sierra Leone, one with a Johnson & Johnson prime-boost vaccine and one with 

a Chinese manufactured vaccine.

In terms of some of the potential strategies for use of Ebola vaccines, for outbreak control there 

are likely to be recommendations for ring vaccination around cases. However, there may be 

other strategies such as vaccination of groups of people in defined geographic areas based on 

the outbreak epidemiology. There are also likely to be recommendations for groups at 

increased risk for Ebola (e.g., HCW, Ebola frontline workers, laboratory workers, and others). 

Consideration also must be given to whether there is a role for vaccination around survivors as 

a way to remain at zero, and whether there is a role for vaccination of the general community.

In thinking about how to use Ebola vaccines, there are scientific and regulatory considerations 

that must be addressed. First, the duration of long-term protection from vaccination must be 

determined. This is particularly relevant for vaccinating HCW, frontline workers, and laboratory 

staff. This applies to those in affected countries, as well as international responders. A 

determination must also be made regarding whether vaccines can be use in special populations 

(e.g., children, pregnant women, HIV-infected persons, and others). Consideration also must be 

given to whether the vaccine can be used for post-exposure prophylaxis (PEP). The vaccines 

are currently available only under an Investigational New Drug (IND) program. Emergency 

licensure through an FDA Emergency Use Authorization (EUA) or a WHO Emergency Use 

Assessment and Listing (EUAL) would increase flexibility and ease of use. Full licensure would 

provide the most flexibility.

There are currently two Ebola vaccine advisory groups. The first is the Global Ebola Vaccine 

Implementation Team (GEVIT), which is a consortium that includes WHO (lead), CDC, United 

Nations International Children's Emergency Fund (UNICEF), Global Alliance for Vaccines and 

Immunization (GAVI), and the Bill & Melinda Gates Foundation. GEVIT’s mandate is 

collaborative planning for the future introduction of Ebola vaccines. At WHO, a SAGE Working 

Group on Ebola Vaccines and Vaccination was formed in November 2014. Over the past year, 

this working group has developed a framework for the use of Ebola vaccines. This framework 

was presented to SAGE on October 20, 2015. The preliminary report from that meeting is that 

SAGE will not make any formal recommendations for vaccine use until it is licensed for either 

emergency use or full licensure. Dr. Goldstein said she also wondered whether ACIP would 

form an Ebola Vaccine WG in the future.

Despite some challenges, STRIVE has been immensely successful. It is providing an 

opportunity to vaccinate over 8500 HCW and frontline workers, with over 5550 vaccinated to 

date. Over 400 Sierra Leonean staff have been trained who are on-the-ground conducting the 

study. Safety and immunogenicity data are being accumulated for vaccine licensure, increasing 

research and response capacity in country, and developing a platform for future vaccine and 

infectious disease research in Sierra Leone. While there is more work to be done, Dr. Goldstein 

believes that Sierra Leone and West Africa are on the road to zero. The hope is that STRIVE 

will contribute to the use of an Ebola vaccine that will prevent what occurred this past year in 

West Africa.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

102 

Discussion Points

Regarding safety in the context of what was found earlier in Guinea and regarding the 

observation in this presentation that no safety signals have been detected in the STRIVE substudy, Dr. Karron said she did not know of a vaccine that does not cause some reaction.

Dr. Goldstein explained that she was not at liberty to present any specific results, so she could 

only be very general at this point. Nothing in the safety sub-study appeared to be any different 

from the safety data that had already been published, and nothing to raise concern among the 

investigators, the DSMB, or the Scientific Steering Committee.

Dr. Romero asked whether children who were exposed during the ring vaccination were offered 

vaccine.

Dr. Goldstein replied that only adults 18 years of age and older were included in the WHO Ring 

Vaccination Trial. When the trial was expanded into Sierra Leone, the age range remained at 

18 years and older. In Guinea, the age range was expanded downward to 15 years of age and 

older. Consideration is being given to lowering the age even further.

Dr. Riley asked whether the STRIVE study excludes pregnant women, and whether a pregnant 

woman in the ring study who had been exposed would not be given the vaccine.

Dr. Goldstein emphasized that the STRIVE trial is different from the WHO Ring Vaccination 

Trial. The STRIVE study excludes pregnant women, and all women between 15 and 49 years 

of age have a urine pregnancy test. Any woman who has a positive pregnancy may not 

participate in the study. Once a participant is enrolled and vaccinated, there are going to be 

some pregnancies and those will be followed. The WHO Ring Vaccination Trial offers women a 

pregnancy test, but the women do not have to have a confirmed negative pregnancy test to 

enroll.

Dr. Ezeanolue wondered why, if children have the greatest lethality, they will not be vaccinated 

if an adult close to them is enrolled in the study who has been exposed and may have 

developed disease.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

103 

Dr. Goldstein clarified that STRIVE is not doing ring vaccination, and that she could not speak 

for the WHO trial other than to say that she knew they were working to decrease the age for 

enrollment into the WHO Ring Trial. STRIVE is pre-exposure prophylaxis of high risk groups 

(HCW, frontline workers, laboratory workers).

Dr. Bennett emphasized that the STRIVE trial is not a ring trial. The WHO trial is ring 

vaccination around a case.

Dr. Riley said she thought Dr. Goldstein said that after the WHO trial was published, if there 

were people in the STRIVE trial who were in the deferred group, they were vaccinated if they 

were a contact.

Dr. Goldstein replied that they were not quite that prescriptive. An enrolled participant in the 

deferred group who has not yet been vaccinated but is at increased risk of exposure, such as 

living in a community where a case has been identified, they are eligible to be vaccinated in 

STRIVE only. That is separate from the ring vaccination. That participant may or may not have 

been included in the ring trial definition of a ring.

Given the concerns about sexual transmission of Ebola, Dr. Reingold wondered whether 

consideration had been given to vaccinating the sexual partners of survivors.

Dr. Goldstein responded that there have been some initial discussions about vaccination of 

sexual contacts of survivors. She thinks that much more must be learned about sexual 

transmission of the disease in terms of how frequently it is sexually transmitted and whether all 

other modes of transmission have been excluded. In the context of the discussions, 

consideration has been given to how easy it is to identify a sexual contact. Who is your sexual 

contact today? How do we know who your sexual contact will be a month from now or six 

months from now? This has raised a discussion of possible geographic vaccination around a 

survivor in the hope of reaching current and possible future sexual contacts who may not be 

identified.

Dr. Reingold quipped that many people know who their current sexual partners are now, but no 

one is certain of who they will be in the future.

Dr. Goldstein noted that HIV and STD experts say that often the formal sexual contact is known, 

but the informal sexual contacts are often not public. If the sexual contact of a sexual contact of 

a survivor today is vaccinated and person X or persons X and Y a month from now, there would 

need to be some mechanism to identify and vaccinate the new sexual contacts. The logistics 

are quite difficult, but this has been discussed. She told Dr. Reingold that he would probably be 

a good person to have on the working group.

Dr. Ezeanolue asked whether there was an express reason that the STRIVE trial did not use the 

ring design that WHO used.

Dr. Goldstein responded that there was a lot of discussion initially as WHO, CDC, and other 

groups were thinking about how to conduct a clinical trial. Nobody knew which study design 

was going to work. There are many ways of conducting trials and reasons for doing so. WHO 

conducted the ring trial, while CDC took responsibility for vaccination of the high risk group of 

HCW, frontline workers, and laboratory workers. 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

104 

Dr. Belongia commended everyone at CDC and everyone in Sierra Leone who worked on-theground on this study, given the difficulty there must have been in implementing a study such as 

this within the circumstances and timeline under which it was done.

Dr. Bennett added that there are many investigators in the US who cannot enroll 100 people for 

an RCT, so this is really amazing.

Dr. Goldstein emphasized that from the beginning, Dr. Schuchat has been a cheerleader for 

STRIVE who ensured them that it would happen, and it did.

Dr. Moore said she was intrigued by the vaccine storage and handling issues, particularly given 

that the vaccine must be stored at -80oC. She asked Dr. Goldstein to speak more about the 

transport, storage, and handling issues in terms of getting the vaccine out to the patients.

Dr. Goldstein confirmed that the vaccine does have to be stored at -80oC. There are three 

vaccine depots, with the main depot being in Freetown. The three main depots have freezers 

that store at -80oC. Constant power sources are needed, which is not easy there. Back-up 

generators were also needed. There must be staff available 24 hours a day. Transport from 

site-to-site was done in an Arktek cooler which kept the vaccine at -80oC. This cooler was

developed as part of a Gates challenge. Once the vaccine was diluted and put into syringes at 

the vaccine depot, it was transported to sites in CryoQ cooler, which kept the vaccine at 2 oC to 

8 oC. The vaccine has to be administered within 8 hours of dilution. Though quite a feat, it 

works quite well.

 Arktek Cooler CryoQ Cooler 

Dr. Moore emphasized how impressive this was, and said she did not know whether this could 

be done in a clinic in the US.

Dr. Neuzil noted that she chaired the Scientific Steering Committee for this trial. She 

congratulated CDC, the many partners, and the hundreds of people on-the-ground in 

Sierra Leone who worked through a very difficult situation. To help people understand, 

the WHO trial in Guinea was a ring vaccination trial, which is an outbreak response 

strategy. Where there were breakthrough cases, those ocurred in the first 7 days. That 

makes sense because that is before the vaccine could have a biologic effect, or when 

the patient was in an incubation period. However, the Sierra Leone trial was a 

preventive strategy for first responders and people who were likely to be exposed. A 

couple of West African countries, Mali and Nigeria, had an incredible response to 

contain this virus. Because Mali is another West African country that has tested two 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

105 

Ebola vaccines, she asked Dr. Mike Levin whether she could coax him to the 

microphone to discuss these for completeness.

 

Dr. Mike Levine (CVD, UM SOM) explained how the WHO Guinea Ring Vaccination trial 

came to exist and how it was designed. With the huge outbreak in three countries 

(Liberia, Sierra Leone, and Guinea), the US government went into Liberia with 

extraordinary resources and had an impact fairly quickly. Sierra Leone is split in a 

competition between who to test and what to test with between the UK and the US. 

Guinea was an orphan. Nobody was showing up to work in Guinea. Guinea asked 

WHO for help, and WHO responded by quickly assembling partners, including the 

Norwegian Institute of Public Health (NIPH). This was key because NIPH quickly 

provided resources to conduct a trial. WHO involved some very senior individuals to 

help with the Ebola outbreak who were French and were able to establish special 

dialogue and communications. WHO convened a couple of planning committees. 

When this was going on, one of the other factors that had not been mentioned was the 

scarcity of doses of vaccine for at least one of the two major vaccines. Even the 

vaccine that was used in Guinea and Sierra Leone was only possible with Big Pharma 

getting involved with NewLink so that many more doses became available. A design 

had to be created that would minimize the number of doses needed, and recognizing 

that the vaccine had to be kept at -80oC. The Arktek was a game-changer 

breakthrough. The cold chain worked well in Guinea and was quite amazing. This 

could not have been done five years ago. The beauty of the ring design is that instead 

of enrolling a large number of individuals and letting Mother Nature or human nature 

determine where the cases of Ebola would be, investigators went to where the cases 

were just as was done in the smallpox eradication days. One of the members of the 

committee ran a smallpox program for the WHO, and a couple of other smallpox 

veterans were on the committee as well, including Dr. Lavine. This design uses a very 

small amount of vaccine. The Norwegians felt that everyone had to receive vaccine for 

ethical reasons, and that was a widely held view in Europe. The elegance of the 

Guinea design, pressured by all of the constraints, was that everybody got vaccine but 

some people got it 21 days later. That is what would occur in a huge outbreak with 

surveillance and containment—not everyone would be receiving vaccine at once. 

Guinea was a “Wild West Show” in terms of having to start from scratch and train 

people very quickly to conduct a trial where there was no infrastructure. The other 

leading candidate vaccine, the chimp adenovirus type 3 (ChAd3), was tested in Mali. 

Particularly for the ChAd3 vaccine, information on how long the vaccine works comes 

from non-human primate studies. This is also true of vesicular stomatitis virus (VSV)-

based vaccine. Those data show that there is 100% protection for several months, but 

then it falls off at 10 months to about 50%. Using the ring design to vaccinate the the 

high risk contacts around cases maximizes what is known about how vaccine works. 

The Mali site was the only one amongst the WHO consortium that involved folks in 

Bethesda and Oxford, and Mali was the only West African site that was able to test the 

vaccine. The highest dose that was used in Mali turned out to be the dose selected for 

large-scale manufacture. Mali had two importations and chains of transmission. The 

second one was a relatively big one. In a sense, it was lucky that it took place in 

Bamako. It was classic shoe leather epidemiology that contained it. Every single 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

106 

contact was identified, put in house quarantine and kept there throughout the 

observation period. In a relatively short period of time, transmission was interrupted. 

There is pretty much an open border between Mali and Guinea and people go back and 

forth. The two importations came from Guinea. Because the individual who brought the 

disease into Bamako was a dignitary, he went to a private hospital instead of going to a 

government health facility. The hospital was thought to be the best care, but it is a 

mystery how they missed his diagnosis. They called it malaria with renal failure, and 

the individual died as did his physician, nurse, and fiancé of the nurse. It was an 

explosion and everyone was very worried. However, with the good leadership of Dr. 

Samba Sow, the Director of the Center for Vaccine Development (CVD-Mali), and a 

good friend of the Ebola Czar of Guinea, every resource went into this effort. Combined 

with shoe leather epidemiology, transmission was interrupted and that is a very special 

legacy.

An unidentified participant commented on the ongoing Guinea trial in an area he 

recently left. Before he left there, the clinical trial expanded the enrollment down to 

participants 7 years of age and older. This information is not shared by the clinical trial 

team, so they asked questions of the contacts to find out who has been vaccinated.

Mara Berger

Parent

It is not unreasonable for all ages of people to be protected with a safe and effective vaccine 

and to be aware that vaccines are available for meningococcal disease for healthy adults 21 to 

55 and healthcare personnel. I’m here today to ask the ACIP to consider recommending the 

conjugate vaccine for routine usage more broadly. My son, Adam Berger, was a 44-year old 

healthy adult enrolled in private teaching hospital in nursing school in Chicago, a very 

prestigious hospital. In 2014, he passed away from the vaccine-preventable meningococcal 

bacterial infectious disease Neisseria meningitides C and sepsis within 16 hours of going to the 

hospital. After Adam passed away, I learned that the nursing registrar never gave him the 

conjugate vaccine to prevent meningococcal disease, nor gave him literature about the disease 

or vaccine because the ACIP and CDC don’t recommend the vaccine for routine usage for 

healthcare personnel with the exception of epidemiologists and adults at increased risk with 

particular medical problems. Therefore, I was devastated to find out that Adam died before his 

time needlessly from a vaccine-preventable infectious disease that we weren’t aware of 

because it was not promoted or talked about. Had Adam and I known about the conjugate

vaccine to prevent meningococcal disease, he would have gotten the shot. Hospitals are 

occupational risks. Knowledge is power and healthy adults and healthcare personnel have the 

right to choose their healthcare based factual medical and vaccine information, even though the 

vaccine isn’t recommended. People cannot be left in the dark about dangerous and deadly 

infectious diseases. The conjugate vaccine is effective, safe, and immunogenic. If the FDA 

approves and licenses a vaccine, doctors can give the shot or send their patients to Walgreen’s 

to receive it. Physicians take an oath to “Do No Harm” and must protect their patients and make 

Public Comment

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

107 

a concerted effort to raise awareness about meningococcal disease and the vaccine to prevent 

it so that adult immunization rates increase.

I believe adults would get the vaccine if their physicians recommended it. Most US adults never 

heard of meningococcal disease or the conjugate vaccine. Medical facilities must also give their 

healthcare workers handouts about the disease and vaccines so that they can make an 

informed decision to reduce their risk from the disease. Adam didn’t have that choice. Many 

insurance companies already pay for the shot as preventive care. In 2015, the FDA licensed 

meningococcal vaccine and it was approved. ACIP recommended it for adolescents 11 to 13. 

In the last decade, thousands of people have contracted the disease and suffered. Ninety-eight 

percent of cases are sporadic all over the United States, many in healthy adults, and two 

percent occur in outbreaks. Perhaps if the vaccine was recommended, adults would get 

vaccinated. Anyone at any time in any place can contract meningococcal disease. Healthy 

adults are just as at increased risk as adults with medical conditions. It’s a fallacy that healthy 

people of any age are immune. Vaccination is the only way to prevent and eradicate 

meningococcal disease. As a matter of fact, the hospital that Adam taught at—I mean that he 

was getting his nursing degree at, I believe he caught the disease when he was doing his 

clinicals. I don’t know if he was wearing a mask, but he was probably taking someone’s heart 

monitoring, got in their face, they spat, coughed, sneezed—I don’t know. But, he got it. We 

don’t know. It was an unknown carrier. A broader recommendation for the vaccine would be a 

wonderful legacy for all of us who lost someone they love. Now the hospital wrote me an email 

that they are giving mandatory meningococcal vaccine shots to all incoming nursing students in 

2016. This is a big deal. So, if you have questions, feel free to contact me at 

maraberger@hotmail.com. Thank you.

Dr. Bennett: Thank you very much, Mrs. Berger, and we are very sad for your loss.

Laurel Wood

Immunization Action Coalition

Thank you. I can’t imagine a much more difficult speaker to follow. So if you’ll forgive me for 

something that may seem a little bit lighter, but in fact, directly relates to the importance of 

giving adult immunizations. In keeping with the ACIP discussions about low adult rates and the 

2000 recommendation for the use of standing orders, the Immunization Action Coalition, in 

conjunction and with support from Pfizer, has developed a program that is occurring all over the 

United States now called “Take a Stand” about the use of standing orders to vaccinate adults 

because we, like you, know that many adult providers have widespread misunderstandings 

about the benefits of using standing orders, as well as many perceived burdens of 

implementation. We have developed this project to offer free workshops on using standing 

orders to raise clinics’ adult immunization rates and streamline their practices. These 

workshops are targeted for clinicians, nurses, and clinical managers in medical practices that 

serve adults. Speakers that are recognized, many of whom have been in this room today, are 

LJ Tan, Bill Atkinson, and Alexandra Stewart of George Washington University. We wanted to 

let you know about this opportunity that may perhaps be coming to a city near you. We have 22 

workshops that have been scheduled. Some have already begun and then we will be 

continuing this through early 2016. So, please take a look at standingorders.org and see if it is 

something that might be of benefit to providers in your area or that you can help us spread the 

word, because we’re all about, as you are, trying to increase adult immunizations as well as 

child immunizations. Thank you very much.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

108 

Dr. Bennett: Thank you very much, and we really appreciate your efforts and knowing about 

them. I think with that we are finished. This is the end of the October 2015 meeting, and I thank 

you all for all of your participation. Safe travels home.

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

109 

 

Upon reviewing the foregoing version of the October 21, 2015 ACIP meeting minutes, Dr. Nancy 

Bennett, ACIP Chair, certified that to the best of her knowledge, they are accurate and 

complete. Her original, signed certification is on file with the Management Analysis and 

Services Office (MASO) of CDC.

Certification

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

110 

CHAIR

BENNETT, Nancy, MD, MS

Professor of Medicine and Public Health Sciences

Director, Center for Community Health

Co-director, Clinical and Translational Science Institute

University of Rochester School of Medicine and Dentistry

Rochester, NY 

Term: 07/01/2015-06/30/2018

ACTING EXECUTIVE SECRETARY

STRIKAS, Raymond, MD, MPH

Centers for Disease Control and Prevention

National Center for Immunization and Respiratory Diseases

Atlanta, GA

MEMBERS

BELONGIA, Edward, MD

Director 

Center for Clinical Epidemiology & Population Health 

Marshfield Clinic Research Foundation

Marshfield, WI

Term: 07/01/2014-06/30/2018

EZEANOLUE, Echezona, MD, MPH 

Professor of Pediatrics and Public Health

Department of Epidemiology and Biostatistics

Director, Global Health and Implementation Research Initiatives

University of Nevada

Las Vegas, NV

Term: 07/01/2015-06/30/2019

HARRIMAN, Kathleen, PhD, MPH, RN

Chief, Vaccine Preventable Disease Epidemiology Section

Immunization Branch

California Department of Public Health

Richmond, CA

Term: 07/01/2012 – 06/30/2016

HARRISON, Lee H., MD 

Professor of Medicine and Epidemiology

Infectious Diseases Epidemiology Research Unit 

University of Pittsburgh

Pittsburgh, PA

Term: 07/01/2012 – 06/30/2016

ACIP Membership Roster

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

111 

KARRON, Ruth A., MD

Professor and Director

Center for Immunization Research 

Department of International Health

Johns Hopkins Bloomberg School of Public Health 

Baltimore, MD

Term: 07/01/2012 – 06/30/2016

KEMPE, Allison, MD, MPH

Professor of Pediatrics

Director of Primary Care Fellowship

University of Colorado School of Medicine

Director of Research

Division of General Academic Pediatrics

Director of Children’s Outcomes Research Program

The Children’s Hospital of Denver

Denver, CO

Term: 07/01/2013 - 06/30/2017

MOORE, Kelly, MD, MPH,

Director, Tennessee Immunization Program 

Tennessee Department of Health 

Assistant Clinical Professor, Department of Health Policy 

Vanderbilt University School of Medicine 

Nashville, TN

Term: 07/01/2015-06/30/2019

PELLEGRINI, Cynthia

Senior Vice President

Public Policy and Government Affairs

March of Dimes

Washington, DC

Term: 07/01/2013-06/30/2017

REINGOLD, Arthur L., MD

Professor of Epidemiology

Edward Penhoet Distinguished for Global Health and Infectious Disease

Associate Dean for Research

School of Public Health

University of California

Berkeley, CA

Term: 07/01/2013-06/30/2017

RILEY, Laura E., MD

Associate Professor, Obstetrics, Gynecology and Reproductive Medicine 

Harvard Medical School 

Maternal Fetal Medicine 

Massachusetts General Hospital

Boston, MA

Term: 07/01/2014-06/30/2018

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

112 

ROMERO, José R., MD, FAAP

Professor of Pediatrics

Horace C. Cabe Endowed Chair in Infectious Diseases

Director, Pediatric Infectious Diseases Section

University of Arkansas for Medical Sciences and Arkansas Children's Hospital 

Director, Clinical Trials Research

Arkansas Children's Hospital Research Institute

Little Rock, AR

Term: 07/01/2014-06/30/2018

RUBIN, Lorry, MD

Director 

Pediatric Infectious Diseases

Steven and Alexandra Cohen Children’s Medical Center of New York

North Shore-Long Island Jewish Health System

New Hyde Park, NY

Professor of Pediatrics, Hofstra-North Shore LIJ School of Medicine

Hempstead, NY

Term: 07/01/2012 – 06/30/2016

STEPHENS, David, MD 

Professor of Medicine, Division of Infectious Diseases 

Chair, Department of Medicine 

Emory University School of Medicine 

Emory University 

Atlanta, GA 

Term: 07/01/2015-06/30/2019

WALTER, Emmanuel (Chip), Jr., MD, MPH

Professor of Pediatrics

Duke University School of Medicine

Durham, NC

Term: 07/01/2015-06/30/2019

EX OFFICIO MEMBERS 

Centers for Medicare and Medicaid Services (CMS)

HANCE, Mary Beth

Senior Policy Advisor

Division of Quality, Evaluations and Health Outcomes

Children and Adults Health Programs Group

Center for Medicaid, CHIP and Survey & Certification

Centers for Medicare and Medicaid Services

Baltimore, MD

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

113 

Department of Defense (DoD)

SERGIENKO, Eric, MD, MPH

CAPT, Medical Corps, United States Navy

Department of Defense Liaison

Centers for Disease Control and Prevention

Atlanta, GA

Department of Veterans Affairs (DVA)

KIM, Jane A., MD, MPH

Deputy Chief Consultant for Preventive Medicine

Office of Patient Care Services

National Center for Health Promotion and Disease Prevention

Durham, North Carolina 

Food and Drug Administration (FDA) 

SUN, Wellington, MD

Director, Division of Vaccines and Related Product Applications

Office of Vaccines Research and Review

Food and Drug Administration

Rockville, MD 

Health Resources and Services Administration (HRSA)

HOUSTON, A. Melissa, MD, MPH, FAAP

Chief Medical Officer

Division of Vaccine Injury Compensation

Health Resources and Services Administration

Rockville, MD

Indian Health Service (IHS)

GROOM, Amy, MPH

Immunization Program Manager

Indian Health Service

Albuquerque, NM

National Vaccine Program Office (NVPO)

GELLIN, Bruce, MD, MPH

Director

National Vaccine Program Office

Department of HHS, Public Health and Science

Washington, DC

National Institutes of Health (NIH)

GORMAN, Richard L., MD

Associate Director for Clinical Research

Division of Microbiology and Infectious Diseases/NIAID

National Institute of Health

Bethesda, MD

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

114 

LIAISON REPRESENTATIVES

American Academy of Family Physicians (AAFP)

SAVOY, Margot, MD, MPH, FAAFP, FABC, CPE

Medical Director, Department of Family & Community Medicine

Christiana Care Health System

Wilmington, DE 

American Academy of Pediatrics (AAP)

BYINGTON, Carrie L., MD

Chair, AAP Committee on Infectious Diseases

H.A. and Edna Benning Presidential Professor of Pediatrics

Associate Vice President for Faculty and Academic Affairs

University of Utah Health Sciences Center

Salt Lake City, UT

American Academy of Pediatrics (AAP)

Red Book Editor 

KIMBERLIN, David, MD

Professor of Pediatrics

Division of Pediatric Infectious Diseases

The University of Alabama at Birmingham School of Medicine

Birmingham, AL

American Academy of Physician Assistants (AAPA)

LÉGER, Marie-Michèle, MPH, PA-C 

Senior Director, Clinical and Health Affairs

American Academy of Physician Assistants

Alexandria, VA

American College Health Association (ACHA)

EVEN, Susan, MD

Executive Director

Student Health Center

University of Missouri

Columbia, MO

American College of Nurse Midwives (ACNM)

HAYES, Carol E., CNM, MN, MPH

Atlanta Perinatal Associates

Atlanta, GA

American College of Nurse Midwives (ACNM) (alternate)

MEHARRY, Pamela M., PHD, CNM

Pregnancy & Birth Center,

Middlesex Hospital, 

Middletown, CT

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

115 

American College of Obstetricians and Gynecologists (ACOG)

AULT, Kevin A., MD, FACOG

Professor and Division Director

Department of Obstetrics and Gynecology

University of Kansas Medical Center 

Kansas City, KS

American College of Physicians (ACP)

FRYHOFER, Sandra Adamson., MD, MACP

Adjunct Associate Professor of Medicine

Emory University School of Medicine

Atlanta, GA

American College of Physicians (ACP) (alternate)

POLAND, Gregory A., MD

Mary Lowell Professor of Medicine and Infectious Diseases

Mayo Clinic 

Rochester, MN

American Geriatrics Society (AGS)

SCHMADER, Kenneth, MD

Professor of Medicine-Geriatrics

Geriatrics Division Chief

Duke University and Durham VA Medical Centers

Durham, NC

America’s Health Insurance Plans (AHIP)

NETOSKIE, Mark J., MD, MBA, FAAP

Market Medical Executive, CIGNA 

Houston, TX

American Medical Association (AMA)

FRYHOFER, Sandra Adamson., MD, MACP

Adjunct Associate Professor of Medicine

Emory University School of Medicine

Atlanta, GA

American Nurses Association (ANA)

RITTLE, Charles (Chad), DNP, MPH, RN, FAAOHN

Assistant Professor, Nursing Faculty

Chatham University, School of Health Sciences

Pittsburgh, PA

American Osteopathic Association (AOA)

GROGG, Stanley E., DO, FACOP

Associate Dean/Professor of Pediatrics

Oklahoma State University-Center for Health Sciences

Tulsa, OK

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

116 

American Pharmacists Association (APhA)

FOSTER, Stephan L., PharmD, FAPhA

Professor and Vice Chair, Department of Clinical Pharmacy

University of Tennessee Health Sciences Center, College of Pharmacy

Memphis, TN

Association of Immunization Managers (AIM)

FINLEY, Christine 

Immunization Program Manager 

Vermont Department of Health

Burlington, VT

Association for Prevention Teaching and Research (APTR)

McKINNEY, W. Paul, MD

Professor and Associate Dean

University of Louisville School of Public Health and Information Sciences

Louisville, KY

Association of State and Territorial Health Officials (ASTHO)

DWELLE, Terry L, MD, MPHTM, FAAP, CPH

State Health Officer

North Dakota Department of Health

Bismarck, ND

Biotechnology Industry Organization (BIO)

ARTHUR, Phyllis A., MBA

Senior Director, Vaccines, Immunotherapeutics and Diagnostics Policy

Washington, DC 

Council of State and Territorial Epidemiologists (CSTE)

HAHN, Christine, MD

State Epidemiologist

Office of Epidemiology, Food Protection and Immunization

Idaho Department of Health and Welfare

Boise, ID

Canadian National Advisory Committee on Immunization (NACI)

GEMMILL, Ian MacDonald, MD, CCFP, FCFP, FRCP(C)

Medical Officer of Health 

Kingston, Frontenac and Lennox & Addington Public Health 

Kingston, Ontario, Canada

Infectious Diseases Society of America (IDSA)

NEUZIL, Kathleen M., MD, MPH, FIDSA

Vaccine Development Global Program (PATH)

Clinical Professor 

Departments of Medicine and Global Health

University of Washington School of Medicine 

Seattle, WA

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

117 

Infectious Diseases Society of America (IDSA) (alternate)

BAKER, Carol J., MD

Professor of Pediatrics

Molecular Virology and Microbiology

Baylor College of Medicine

Houston, TX

National Association of County and City Health Officials (NACCHO)

ZAHN, Matthew, MD

Medical Director, Epidemiology

Orange County Health Care Agency

Santa Ana, CA

National Association of County and City Health Officials (NACCHO) (alternate)

DUCHIN, Jeffrey, MD

Health Officer and Chief, Communicable Disease Epidemiology and Immunization Section 

Public Health - Seattle and King County

Professor in Medicine 

Division of Allergy and Infectious Diseases

University of Washington School of Medicine and School of Public Health

Seattle, WA

National Association of Pediatric Nurse Practitioners (NAPNAP)

STINCHFIELD, Patricia A., RN, MS, CPNP

Director

Infectious Disease/Immunology/Infection Control 

Children's Hospitals and Clinics of Minnesota

St. Paul, MN

National Foundation for Infectious Diseases (NFID)

SCHAFFNER, William, MD

Chairman, Department of Preventive Medicine

Vanderbilt University School of Medicine

Nashville, TN

National Immunization Council and Child Health Program, Mexico

VILLASEÑOR RUIZ, Ignacio

Directora del Programa de Atencion da la Salud de la Infancia y la Adolescencia / Director 

General, Child and Adolescent Health

Centro Nacional Para la Salud de la Infancia Y La Adolescencia / National Center for Child and 

Adolescent Health

Ministry of Health / Secretaría de Salud

Mexico

National Medical Association (NMA)

WHITLEY-WILLIAMS, Patricia, MD

Professor and Chair

University of Medicine and Dentistry of New Jersey

Robert Wood Johnson Medical School 

New Brunswick, NJ

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

118 

National Vaccine Advisory Committee (NVAC)

ORENSTEIN, Walter, MD

Chair, NVAC 

Associate Director, Emory Vaccine Center

Emory University

Atlanta, GA

Pediatric Infectious Diseases Society (PIDS)

SAWYER, Mark H, MD

Professor of Clinical Pediatrics

University of California, San Diego School of Medicine

San Diego, CA

Pediatric Infectious Diseases Society (PIDS) (alternate)

ENGLUND, Janet A., MD 

Professor, Department of Pediatrics

Seattle Children's Hospital

University of Washington

Seattle, WA

Pharmaceutical Research and Manufacturers of America (PhRMA)

JOHNSON, David R, MD, MPH 

Associate Vice President, Global Medical Affairs, Sanofi Pasteur 

Swiftwater, PA

Society for Adolescent Health and Medicine (SAHM)

MIDDLEMAN, Amy B., MD, MSEd, MPH

Professor of Pediatrics 

Chief, Section of Adolescent Medicine

University of Oklahoma Health Sciences Center

Oklahoma City, OK

Society for Healthcare Epidemiology of America (SHEA)

WEBER, David, MD, MPH

Professor of Medicine, Pediatrics, and Epidemiology

University of North Carolina Schools of Medicine and Public Health

Medical Director, Hospital Epidemiology and Occupational Health, UNC Health Care

University of North Carolina

Chapel Hill, NC

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

119 

September 8, 2015

To: Sylvia Burwell, United States Secretary of Health & Human Services

cc: Dr. Thomas Frieden, Director of the CDC

cc: ACIP Committee

Dear Secretary Burwell,

I researched meningococcal disease and conjugate vaccines thoroughly and spoke during public 

comments at the June 2015 ACIP meeting in Atlanta. I told the ACIP committee to recommend 

the conjugate vaccines Menactra and Menveo which protect from meningococcal disease 

Neisseria meningitidis bacterial strains A, C, Y and W135, but it wasn’t on their agenda. The 

“unprotected” must be protected, healthy adults (HA) 21-55 and healthcare personnel (HCP). 

Anyone at any time and any place can contract meningococcal disease! Meningococcal disease 

isn’t just for children and it doesn’t stop at the dorm. The average age to contract the disease is 

45 and male and women contract it too. I implore you to treat meningococcal disease as though 

it were Ebola when protocols and policies were revised and put into place quickly with the first US 

Ebola case of a nurse in Houston. I’m urging you to insist that the ACIP add the conjugate 

vaccines Menactra and Menveo to their October 21, 2015 agenda and to recommend the 

vaccines for routine use for healthy adults 21-55 years old and to highly recommend routine 

vaccinations for all healthcare personnel who wish to reduce their risk from meningococcal 

disease. I have hundreds of medical reports and articles from independent infectious disease 

experts that conflict with those of the ACIP. Knowledge is power and being informed about a 

vaccine preventable infectious disease vaccine is the only way to prevent and eradicate 

potentially deadly meningococcal disease. Physicians must “do no harm.” In my opinion, the 

current ACIP and their predecessors must take responsibility for their irrational decisions to not 

recommend an available vaccine to prevent meningococcal disease, which would have saved the 

lives of healthy adults and healthcare personnel for the past ten years. Health policies have to 

change. This is a very serious matter. 

If you remember from my letter on May 14, 2015, my son Adam was a 44 year old healthy adult 

enrolled in a private teaching hospital/nursing school in Chicago. In 2014, Adam passed away 

within hours from the vaccine preventable infectious disease Neisseria meningitidis C/sepsis, 

needlessly! Adam received all the required vaccinations for nursing school. But, the nursing 

registrar never mentioned a Menactra vaccination for meningococcal disease because the ACIP 

and CDC have not recommended Menactra for routine use for healthy adults 21-55 years old and 

healthcare personnel with the exception of epidemiologists. Most healthy adults 21-55 don’t even

know what meningococcal disease is or that there’s a vaccine to prevent it. Therefore, Adam 

wasn’t informed about the disease and vaccine to protect himself and died before his time! My 

son’s death was a senseless tragedy and our family’s grief is beyond recovery or adjusting. 

Appendix A: Public Comment Letter

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

120 

Primary care physicians should give their healthy adults and medical facilities should give their 

healthcare personnel meningococcal disease literature and vaccine information so that they can 

make an informed decision about wanting to receive the vaccine to reduce their risk from the 

disease even though the ACIP and CDC don’t recommend the vaccine. The ACIP cannot keep 

the lid on meningococcal disease and the vaccine to prevent it anymore. The jig is up as they 

say. The FDA approved and licensed Menactra in January 2005 for routine use in 9 month-55 

year olds. The fact is that once the FDA approves and licenses a vaccine for routine use for a 

particular age group, those individuals can get vaccinated even if the ACIP and CDC don’t 

recommend the vaccine. It’s not forbidden to get vaccinated as most adults believe. In fact, if 

the disease and vaccine literature were available, anyone can go to Walgreen’s and get 

vaccinated if internists and primary care physicians don’t want to store or supply the vaccine.

 

The ACIP must recommend the meningococcal vaccines to ensure that all insurance companies 

will be required to cover the cost. Currently, even without the ACIP’s non- recommendation, most 

insurance companies do cover the cost of Menactra, which is approx. $140 and they consider it 

“preventative care.” But, there are some insurance companies that don’t cover the cost. Even 

The Affordable Care Act pays for the vaccinations for families including children and college 

students up to 26 years of age.

 

Patients rely on their primary care physician for accurate medical advice. Since Menactra isn’t 

recommended, many doctors think it’s prohibitive to vaccinate healthy adults or haven’t kept up 

on meningococcal disease and don’t discuss it with them. It’s a “don’t ask” “don’t tell” situation. 

Most healthy adult patients 21-55 never heard of meningococcal disease, so they don’t ask. Or, 

if they have heard of meningococcal disease, they may believe that they don’t qualify to receive 

the vaccine because they don’t have medical problems on “at increased risk” list, so they don’t 

ask and forget about it. They may also have a false sense of security and believe that because 

they’re healthy, they won’t contract the disease! The CDC focuses on babies, children, 

adolescents and college students and the elderly over 64 years old. The CDC states on its 

meningitis pages that routine vaccination is not recommended for 21-55 year olds. The ACIP 

writes that the vaccine is not routinely recommended for healthcare personnel.

 

Healthcare personnel, paramedics and firemen have contracted meningococcal disease. 

Everyone knows that hospitals are occupational risks and endemic full of bacteria and sick 

patients. That’s where Adam caught the disease. A perfectly healthy adult 21-55 or healthcare 

personnel can contract meningococcal disease from an unknown carrier who carries Neisseria 

bacteria in their nasal cavity or throat and then spews respiratory droplets such as a sneeze, 

cough or spit within three feet of a healthy adult or healthcare personnel. Carriers are 

approximately 20% of the general population in the United States and don’t contract the disease 

or may not even know they’re carriers. That is precisely why no one is immune to this insidious 

disease unless they get vaccinated. 

Meningococcal disease – Neisseria meningitidis C is the leading infectious disease in the United 

States. It is serious and potentially deadly especially with sepsis the number one illness in the 

United States. Healthy adults who contract Neisseria meningitidis and sepsis can die within 

hours. Healthy adults are just as “at increased risk” as adults with medical conditions because 

natural antibodies wane as children grow into healthy adults. That’s why there’s a vaccine to 

boost immunity in adults, but it’s not recommended! Therefore healthy adults 21-55 and 

healthcare personnel who were never vaccinated, under vaccinated or received the 

polysaccharide Menomune more than three years ago or conjugates Menactra or Menveo 

vaccines more than 5 years ago may be due for a booster vaccine now. 

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

121 

Neisseria meningitidis C has increased for four decades. The CDC wrote that meningococcal 

vaccination in adults is low and that the disease has not decreased in adults, which is correct. 

The propaganda that meningococcal disease is rare must be debunked! The CDC states that in 

the US approx. 98% of cases of meningococcal disease are sporadic all over the United States, 

which is correct. Other experts in the field say that currently the disease causes approximately 

3,000 reported cases and that many cases go unreported. Outbreaks continue to occur. There 

were approximately 69 outbreaks identified in the US between 1994 and 2002, most of which 

were Neisseria meningitidis strain C. Between 2005 and 2015 approximately 20,000 people 

contracted meningococcal disease and the ACIP turned a blind eye.

 

Since 2002, there have been additional outbreaks of strain C as you’ve seen in the newspapers 

and TV. Controlling outbreaks is useless, which is like putting gas on a fire. Vaccinations must 

be given before an outbreak, which would increase herd immunity. It makes no sense to vaccinate 

after an outbreak in which it’s an open invitation for individuals to contract the disease and become 

maimed or die. When is it going to end? Meningococcal disease is life-threatening and can 

cause sequelae or death in previously healthy adults and healthcare personnel. Between 2003 

and 2007, the CDC wrote that 4,100 people contracted meningococcal disease annually. With 

that being said, weren’t 4,100 cases in 2005 enough for the ACIP to recommend Menactra to 

healthy adults 21-55 year olds and healthcare personnel? Apparently not, because just before 

Menactra was about to become available in 2005, the ACIP wrote “that for unknown reasons, 

incidence has declined since the peak of disease in the late 1990s.” Then they just cut off the 

vaccine from healthy adults altogether and instead only recommended Menactra to adolescents. 

The ACIP failed to state that incidence of Neisseria meningitidis C did not decline, which Menactra 

would have prevented!

 

In 2006, the Menactra vaccine supply decreased and the ACIP then prioritized again and 

recommended the vaccine to adults “at increased risk” with a caveat of medical conditions, which 

excluded healthy adults.

 

In 2007, when Menactra’s supply increased, the ACIP still didn’t recommend Menactra to healthy 

adults 21-55 and hasn’t to date! Was the reason just bureaucratic indifference? The ACIP should

never have been oppositional to recommending Menactra, which was proven to be safe, 

immunogenic and effective by the FDA. It’s cost effective too!

I’m wondering why the CDC, AMA, IDSA and other medical professionals around the country 

haven’t challenged the ACIP about excluding healthy adults 21-55 and healthcare personnel from 

Menactra vaccine based on lame excuses and certainly not for medical reasons.

 

I went to Adam’s former nursing school and gave the nursing director and infectious disease 

doctor a lesson about meningococcal disease strain C. They recently wrote me that all incoming 

2016 nursing students must have mandatory conjugate Menactra vaccinations.

 

In conclusion, I appreciate your attention in this matter. I’m going to honor my beautiful son Adam 

and in his memory create awareness through any means possible about meningococcal disease 

and the conjugate vaccines that prevents it. This endeavor is called “The Adam Berger 

Meningococcal Disease and Vaccination Information Initiative.”

This document has been archived for historical purposes. (11/1/2015)
Advisory Committee on Immunization Practices (ACIP) Summary Report October 21, 2015

122 

Please contact me if you so choose.

 

Thank you. 

Mara Berger 

5801 N. Sheridan Road, 5B 

Chicago, IL 60660 

Email: maraberger@hotmail.com

This document has been archived for historical purposes. (11/1/2015)